Inovelon Tablets: Indications, Dosage, Precautions, Adverse Effects
Россия
  • Россия
  • Украина

Inovelon Tablets - Product Information

Manufacture: Eisai Inc.
Country: Great Britain
Condition: Lennox-Gastaut Syndrome, Seizures (Convulsions)
Class: Anticonvulsants
Form: Tablets
Ingredients: rufinamide, lactose monohydrate, microcrystalline cellulose, maize starch, croscarmellose sodium, hypromellose, magnesium stearate, sodium laurilsulfate and colloidal anhydrous silica. The film-coating consists hypromellose, macrogols (8000), titanium dioxide (E171), talc and ferric oxide red (E172)

Name of the Medicinal Product

  • 100 mg: Inovelon 100 mg filmcoated tablets.
  • 200 mg: Inovelon 200 mg filmcoated tablets.
  • 400 mg: Inovelon 400 mg filmcoated tablets.
  • 40 mg/ml: Inovelon 40 mg/ml oral suspension.

Qualitative and Quantitative Composition

Film Coated Tablets

  • 100 mg: Each filmcoated tablet contains 100 mg rufinamide.
    • Excipient with known effect: each film coated tablet contains 20 mg lactose monohydrate
  • 200 mg: Each filmcoated tablet contains 200 mg rufinamide.
    • Excipient with known effect: each film coated tablet contains 40 mg lactose monohydrate
  • 400 mg: Each filmcoated tablet contains 400 mg rufinamide.
    • Excipient with known effect: each film coated tablet contains 80 mg lactose monohydrate

Oral Suspension

Each ml of oral suspension contains 40 mg rufinamide.

1 bottle of 460 ml contains 18400 mg rufinamide.

Excipients with known effect

Each ml of oral suspension contains 1.2 mg methyl parahydroxybenzoate (E218), 0.3 mg propyl parahydroxybenzoate (E216) and 250 mg sorbitol (E420).

For the full list of excipients, see List of excipients.

Pharmaceutical Form

Filmcoated Tablets

  • 100 mg: Pink, ’ovaloid’, slightly convex, scored on both sides, embossed ’Є261’ on one side and blank on the other side.
  • 200 mg: Pink, ’ovaloid’, slightly convex, scored on both sides, embossed ’Є262’ on one side and blank on the other side.
  • 400 mg: Pink, ’ovaloid’, slightly convex, scored on both sides, embossed ’Є263’ on one side and blank on the other side.

The tablets can be divided into equal doses.

Oral Suspension

White slightly viscous suspension.

Clinical Particulars

Therapeutic Indications

Inovelon is indicated as adjunctive therapy in the treatment of seizures associated with LennoxGastaut syndrome in patients 4 years of age and older.

Posology and Method of Administration

Treatment with rufinamide should be initiated by a physician specialised in paediatrics or neurology with experience in the treatment of epilepsy.

Inovelon oral suspension and Inovelon film coated tablets may be interchanged at equal doses. Patients should be monitored during the switch over period.

Posology

Use in children four years of age or older and less than 30 kg

Patients <30 kg not receiving valproate

Treatment should be initiated at a daily dose of 200 mg (5 ml dosing suspension given as two 2.5 ml doses, one in the morning and one in the evening). According to clinical response and tolerability, the dose may be increased by 200 mg/day increments, as frequently as every two days, up to a maximum recommended dose of 1000 mg/day (25 ml/day). Doses of up to 3600 mg/day (90 ml/day) have been studied in a limited number of patients.

Patients <30 kg also receiving valproate

As valproate significantly decreases clearance of rufinamide, a lower maximum dose of Inovelon is recommended for patients <30 kg being coadministered valproate. Treatment should be initiated at a daily dose of 200 mg. According to clinical response and tolerability, after a minimum of 2 days the dose may be increased by 200 mg/day, to the maximum recommended dose of 600 mg/day (15 ml/day).

Use in adults, adolescents and children four years of age or older of 30 kg or over

Treatment should be initiated at a daily dose of 400 mg (10 ml dosing suspension given as two 5 ml doses). According to clinical response and tolerability, the dose may be increased by 400 mg/day increments, as frequently as every two days, up to a maximum recommended dose as indicated in the table below.

Weight range 30.0 – 50.0 kg 50.1 – 70.0 kg ≥70.1 kg
Maximum recommended dose 1,800 mg/day or 45 ml/day 2,400 mg/day or 60 ml/day 3,200 mg/day or 80 ml/day

Doses of up to 4,000 mg/day (100 ml/day) in the 3050 kg range or 4,800 mg/day (120 ml/day) in the over 50 kg category have been studied in a limited number of patients.

Discontinuation of treatment

When rufinamide treatment is to be discontinued, it should be withdrawn gradually. In clinical trials rufinamide discontinuation was achieved by reducing the dose by approximately 25% every two days.

In the case of one or more missed doses, individualised clinical judgement is necessary.

Uncontrolled openlabel studies suggest sustained longterm efficacy, although no controlled study has been conducted for longer than three months.

Paediatric population

The safety and efficacy of rufinamide of children aged 4 years and less have not yet been established. No data are available.

Older people

There is limited information on the use of rufinamide in older people. Since, the pharmacokinetics of rufinamide are not altered in older people (see Pharmacokinetic properties), dosage adjustment is not required in patients over 65 years of age.

Renal impairment

A study in patients with severe renal impairment indicated that no dose adjustments are required for these patients (see Pharmacokinetic properties).

Hepatic impairment

Use in patients with hepatic impairment has not been studied. Caution and careful dose titration is recommended when treating patients with mild to moderate hepatic impairment. Therefore, use in patients with severe hepatic impairment is not recommended.

Method of administration

Rufinamide is for oral use. It should be taken twice daily with water in the morning and in the evening, in two equally divided doses. As a food effect was observed, it will preferable to should be administered with food (see Pharmacokinetic properties).

Film Coated Tablets

If the patient has difficulty with swallowing, tablets can be crushed and administered in half a glass of water.

Oral Suspension

The oral suspension should be shaken vigorously before every administration. Please refer to Special precautions for disposal and other handling for further details.

Contraindications

Hypersensitivity to the active substance, triazole derivatives or to any of the excipients listed in List of excipients.

Special Warnings and Precautions for Use

Status epilepticus

Status epilepticus cases have been observed during clinical development studies, under rufinamide whereas no such cases have been observed under placebo. These events led to rufinamide discontinuation in 20 % of the cases. If patients develop new seizure types and/or experience an increased frequency of status epilepticus that is different from the patient's baseline condition, then the benefit risk ratio of the therapy should be reassessed.

Withdrawal of rufinamide

Rufinamide should be withdrawn gradually to reduce the possibility of seizures on withdrawal. In clinical studies discontinuation was achieved by reducing the dose by approximately 25% every two days. There are insufficient data on the withdrawal of concomitant antiepileptic medicinal products once seizure control has been achieved with the addition of rufinamide.

Central Nervous System reactions

Rufinamide treatment has been associated with dizziness, somnolence, ataxia and gait disturbances, which could increase the occurrence of accidental falls in this population (see Pharmacokinetic properties). Patients and carers should exercise caution until they are familiar with the potential effects of this medicinal product.

Hypersensitivity reactions

Serious antiepileptic medicinal product hypersensitivity syndrome including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) and StevensJohnson syndrome have occurred in association with rufinamide therapy. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. Other associated manifestations included lymphadenopathy, liver function tests abnormalities, and haematuria. Because the disorder is variable in its expression, other organ system signs and symptoms not noted here may occur. The antiepileptic drug hypersensitivity syndrome occurred in close temporal association to the initiation of rufinamide therapy and in the paediatric population. If this reaction is suspected, rufinamide should be discontinued and alternative treatment started. All patients who develop a rash while taking rufinamide must be closely monitored.

QT shortening

In a thorough QT study, rufinamide produced a decrease in QTc interval proportional to concentration. Although the underlying mechanism and safety relevance of this finding is not known, clinicians should use clinical judgment when assessing whether to prescribe rufinamide to patients at risk from further shortening their QTc duration (eg. Congenital Short QT Syndrome or patients with a family history of such a syndrome).

Women of childbearing potential

Women of childbearing potential must use contraceptive measures during treatment with Inovelon. Physicians should try to ensure that appropriate contraception is used, and should use clinical judgement when assessing whether oral contraceptives, or the doses of the oral contraceptive components, are adequate based on the individual patients clinical situation (see Interaction with other medicinal products and other forms of interaction).

Lactose

Inovelon contains lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption should not take this medicine.

Parahydroxybenzoates, Sorbitol

Inovelon oral suspension contains parahydroxybenzoates which may cause allergic reactions (possibly delayed). It also contains sorbitol and, therefore, should not be administered to patients with rare hereditary problems of fructose intolerance.

Suicidal ideation

Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications. A metaanalysis of randomised placebocontrolled trials of antiepileptic medicinal products has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for Inovelon.

Therefore patients should be monitored for signs of 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 suicidal ideation or behaviour emerge.

Interaction With Other Medicinal Products and Other Forms of Interaction

Potential for other medicinal products to affect rufinamide

Other antiepileptic medicinal products

Rufinamide concentrations are not subject to clinically relevant changes on coadministration with known enzyme inducing antiepileptic medicinal products.

For patients on rufinamide treatment who have administration of valproate initiated, significant increases in rufinamide plasma concentrations may occur. The most pronounced increases were observed in patients of low body weight (<30 kg). Therefore, consideration should be given to a dose reduction of Inovelon in patients <30 kg who are initiated on valproate therapy (see Posology and method of administration).

The addition or withdrawal of these medicinal products or adjusting of the dose of these medicinal products during rufinamide therapy may require an adjustment in dosage of rufinamide.

No significant changes in rufinamide concentration are observed following coadministration with lamotrigine, topiramate or benzodiazepines.

Potential for rufinamide to affect other medicinal products

Other antiepileptic medicinal products

The pharmacokinetic interactions between rufinamide and other antiepileptic medicinal products have been evaluated in patients with epilepsy using population pharmacokinetic modelling. Rufinamide appears not to have clinically relevant effect on carbamazepine, lamotrigine, phenobarbital, topiramate, phenytoin or valproate steady state concentrations.

Oral contraceptives

Coadministration of rufinamide 800mg b.i.d. and a combined oral contraceptive (ethinyloestradiol 35µg and norethindrone 1mg) for 14 days resulted in a mean decrease in the ethinyl estradiol AUC0-24 of 22% and in norethindrone AUC0-24 of 14%. Studies with other oral or implant contraceptives have not been conducted. Women of childbearing potential using hormonal contraceptives are advised to use an additional safe and effective contraceptive method (see Special warnings and precautions for use and Fertility, pregnancy and lactation).

Cytochrome P450 enzymes

Rufinamide is metabolised by hydrolysis, and is not metabolised to any notable degree by cytochrome P450 enzymes. Furthermore, rufinamide does not inhibit the activity of cytochrome P450 enzymes (see Pharmacokinetic properties). Thus, clinically significant interactions mediated through inhibition of cytochrome P450 system by rufinamide are unlikely to occur. Rufinamide has been shown to induce the cytochrome P450 enzyme CYP3A4 and may therefore reduce the plasma concentrations of substances which are metabolised by this enzyme. The effect was modest to moderate. The mean CYP3A activity, assessed as clearance of triazolam, was increased by 55% after 11 days of treatment with rufinamide 400 mg b.i.d. The exposure of triazolam was reduced by 36%. Higher rufinamide doses may result in a more pronounced induction. It may not be excluded that rufinamide may decrease the exposure of substances metabolized by other enzymes, or transported by transport proteins such as Pglycoprotein.

It is recommended that patients treated with substances that are metabolised by the CYP3A enzyme system are to be carefully monitored for two weeks at the start of, or after the end of treatment with rufinamide, or after any marked change in the dose. A dose adjustment of the concomitantly administered medicinal product may need to be considered. These recommendations should also be considered when rufinamide is used concomitantly with substances with a narrow therapeutic window such as warfarin and digoxin.

A specific interaction study in healthy subjects revealed no influence of rufinamide at a dose of 400 mg bid on the pharmacokinetics of olanzapine, a CYP1A2 substrate.

No data on the interaction of rufinamide with alcohol are available.

Fertility, Pregnancy and Lactation

Pregnancy

Risk related to epilepsy and antiepileptic medicinal products in general

It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population. In the treated population, an increase in malformations has been noted with polytherapy; however, the extent to which the treatment and/or the illness is responsible has not been elucidated.

Moreover, effective antiepileptic therapy must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.

Risk related to rufinamide

Studies in animals revealed no teratogenic effect but foetotoxicity in presence of maternal toxicity (see Preclinical safety data). The potential risk for humans is unknown.

For rufinamide, no clinical data on exposed pregnancies are available.

Taking these data into consideration, rufinamide should not be used during pregnancy unless clearly necessary and in women of childbearing age not using contraceptive measures.

Women of childbearing potential must use contraceptive measures during treatment with rufinamide. Physicians should try to ensure that appropriate contraception is used, and should use clinical judgement when assessing whether oral contraceptives, or the doses of the oral contraceptive components, are adequate based on the individual patients clinical situation (see Interaction with other medicinal products and other forms of interaction).

If women treated with rufinamide plan to become pregnant, the indication of this product should be carefully weighed. During pregnancy, an effective antiepileptic rufinamide treatment must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.

Breastfeeding

It is not known if rufinamide is excreted in human breast milk. Due to the potential harmful effects for the breast fed infant, breastfeeding should be avoided during maternal treatment with rufinamide.

Fertility

No data are available on the effects on fertility following treatment with rufinamide

Effects on Ability to Drive and Use Machines

Inovelon may cause dizziness, somnolence and blurred vision. Depending on the individual sensitivity, rufinamide may have a mild to major influence on the ability to drive and use machines. Patients must be advised to exercise caution during activities requiring a high degree of alertness, e.g., driving or operating machinery.

Undesirable Effects

Summary of the safety profile

The clinical development program has included over 1,900 patients, with different types of epilepsy, exposed to rufinamide. The most commonly reported adverse reactions overall were headache, dizziness, fatigue, and somnolence. The most common adverse reactions observed at a higher incidence than placebo in patients with LennoxGastaut syndrome were somnolence and vomiting. Adverse reactions were usually mild to moderate in severity. The discontinuation rate in LennoxGastaut syndrome due to adverse reactions was 8.2% for patients receiving rufinamide and 0% for patients receiving placebo. The most common adverse reactions resulting in discontinuation from the rufinamide treatment group were rash and vomiting.

Tabulated list of adverse reactions

Adverse reactions reported with an incidence greater than placebo, during the LennoxGastaut syndrome doubleblind studies or in the overall rufinamideexposed population, are listed in the table below by MedDRA preferred term, system organ class and by frequency.

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 < 1/10), uncommon (≥ 1/1,000 < 1/100), rare (≥1/10,000 to <1/1,000).

System Organ Class Very Common Common Uncommon Rare
Infections and Infestations Pneumonia
Influenza
Nasopharyngitis
Ear infection
Sinusitis
Rhinitis
Immune system disorders Hypersensitivity*
Metabolism and nutrition disorders Anorexia
Eating disorder
Decreased appetite
Psychiatric disorders Anxiety
Insomnia
Nervous system disorders Somnolence* Status epilepticus*
Headache Convulsion
Dizziness* Coordination Abnormal*
Nystagmus
Psychomotor hyperactivity
Tremor
Eye Disorders Diplopia
Vision blurred
Ear and Labyrinth disorders Vertigo
Respiratory, thoracic and mediastinal disorders Epistaxis
Gastrointestinal disorders Nausea Abdominal pain upper
Vomiting Constipation
Dyspepsia
Diarrhoea
Hepatobiliary disorders Hepatic enzyme increase
Skin and subcutaneous tissue disorders Rash*
Acne
Musculoskeletal and connective tissue and bone disorders Back pain
Reproductive system and breast disorders Oligomenorrhoea
General disorders and administration site conditions Fatigue Gait disturbance*
Investigations Weight decrease
Injury, poisoning and procedural complications Head injury
Contusion

*Cross refer to Special warnings and precautions for use

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. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website:www.mhra.gov.uk/yellowcard

Overdose

After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis. There is no specific antidote for rufinamide. Treatment should be supportive and may include haemodialysis (see Pharmacokinetic properties).

Multiple dosing of 7,200 mg/day was associated with no major signs or symptoms.

Pharmacological Properties

Pharmacodynamic Properties

Pharmacotherapeutic group: antiepileptics, carboxamide derivatives; ATCcode: N03AF03.

Mechanism of action

Rufinamide modulates the activity of sodium channels, prolonging their inactive state. Rufinamide is active in a range of animal models of epilepsy.

Clinical experience

Inovelon (rufinamide tablets) was administered in a double blind, placebocontrolled study, at doses of up to 45 mg/kg/day for 84 days, to 139 patients with inadequately controlled seizures associated with LennoxGastaut Syndrome (including both atypical absence seizures and drop attacks). Male or female patients (between 4 and 30 years of age) were included if they were being treated with 1 to 3 concomitant fixeddose antiepileptic medicinal products. Each patient had to have at least 90 seizures in the month prior to study entry. A significant improvement was observed for all three primary variables: the percentage change in total seizure frequency per 28 days during the maintenance phase relative to baseline (35.8% on Inovelon vs. –1.6% on placebo, p= 0.0006), the number of tonicatonic seizures (42.9% on Inovelon vs. 2.2% on placebo, p = 0.0002), and the seizure severity rating from the Global Evaluation performed by the parent/guardian at the end of the doubleblind phase (much or very much improved in 32.2% on Inovelon vs. 14.5% on the placebo arm, p=0.0041).

Population pharmacokinetic/pharmacodynamic modelling demonstrated that the reduction of total and tonicatonic seizure frequencies, the improvement of the global evaluation of seizure severity and the increase in probability of reduction of seizure frequency were dependent on rufinamide concentrations.

Pharmacokinetic Properties

Absorption

Maximum plasma levels are reached approximately 6 hours after administration. Peak concentration (Cmax ) and plasma AUC of rufinamide increase less than proportionally with doses in both fasted and fed healthy subjects and in patients, probably due to doselimited absorption behaviour. After single doses food increases the bioavailability (AUC) of rufinamide by approximately 34% and the peak plasma concentration by 56%.

Inovelon oral suspension and Inovelon film coated tablets have been demonstrated to be bioequivalent.

Distribution

In in-vitro studies, only a small fraction of rufinamide (34%) was bound to human serum proteins with albumin accounting for approximately 80% of this binding. This indicates minimal risk of drugdrug interactions by displacement from binding sites during concomitant administration of other substances. Rufinamide was evenly distributed between erythrocytes and plasma.

Biotransformation

Rufinamide is almost exclusively eliminated by metabolism. The main pathway of metabolism is hydrolysis of the carboxylamide group to the pharmacologically inactive acid derivative CGP 47292. Cytochrome P450mediated metabolism is very minor. The formation of small amounts of glutathione conjugates cannot be completely excluded.

Rufinamide has demonstrated little or no significant capacity in-vitro to act as a competitive or mechanismbased inhibitor of the following human P450 enzymes: CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5 or CYP4A9/112.

Elimination

The plasma elimination halflife is approximately 610 hours in healthy subjects and patients with epilepsy. When given twice daily at 12hourly intervals, rufinamide accumulates to the extent predicted by its terminal halflife, indicating that the pharmacokinetics of rufinamide are timeindependent (i.e. no autoinduction of metabolism).

In a radiotracer study in three healthy volunteers, the parent compound (rufinamide) was the main radioactive component in plasma, representing about 80% of the total radioactivity, and the metabolite CGP 47292 constituting only about 15%. Renal excretion was the predominant route of elimination for active substance related material, accounting for 84.7% of the dose.

Linearity/nonlinearity

The bioavailability of rufinamide is dependent on dose. As dose increases the bioavailability decreases.

Pharmacokinetics in special patient groups

Sex

Population pharmacokinetic modelling has been used to evaluate the influence of sex on the pharmacokinetics of rufinamide. Such evaluations indicate that sex does not affect the pharmacokinetics of rufinamide to a clinically relevant extent.

Renal impairment

The pharmacokinetics of a single 400 mg dose of rufinamide were not altered in subjects with chronic and severe renal failure compared to healthy volunteers. However, plasma levels were reduced by approximately 30% when haemodialysis was applied after administration of rufinamide, suggesting that this may be a useful procedure in case of overdose (see Posology and method of administration and Overdose).

Hepatic impairment

No studies have been performed in patients with hepatic impairment and therefore Inovelon should not be administered to patients with severe hepatic impairment (see Posology and method of administration).

Children (2-12 years)

Children generally have lower clearance of rufinamide than adults, and this difference is related to body size. Studies in newborn infants or infants and toddlers under 2 years of age have not been conducted.

Older people

A pharmacokinetic study in older healthy volunteers did not show a significant difference in pharmacokinetic parameters compared with younger adults.

Preclinical Safety Data

Conventional safety pharmacology studies revealed no special hazards at clinically relevant doses.

Toxicities observed in dogs at levels similar to human exposure at the maximum recommended dose were liver changes, including bile thrombi, cholestasis and liver enzyme elevations thought to be related to increased bile secretion in this species. No evidence of an associated risk was identified in the rat and monkey repeat dose toxicity studies.

In reproductive and developmental toxicity studies, there were reductions in foetal growth and survival, and some stillbirths secondary to maternal toxicity. However, no effects on morphology and function, including learning or memory, were observed in the offspring. Rufinamide was not teratogenic in mice, rats or rabbits.

Rufinamide was not genotoxic and had no carcinogenic potential. Adverse effects not observed in clinical studies, but seen in animals at exposure levels similar to clinical exposure levels and with possible relevance to human use was myelofibrosis of the bone marrow in the mouse carcinogenicity study. Benign bone neoplasms (osteomas) and hyperostosis seen in mice were considered a result of the activation of a mouse specific virus by fluoride ions released during the oxidative metabolism of rufinamide.

Regarding the immunotoxic potential, small thymus and thymic involution were observed in dogs in a 13week study with significant response at the high dose in male. In the 13 week study, female bone marrow and lymphoid changes are reported at the high dose with a weak incidence. In rats decreased cellularity of the bone marrow and thymic atrophy were observed only in the carcinogenicity study.

Pharmaceutical Particulars

List of Excipients

Film Coated Tablet Core

  • Lactose monohydrate
  • Cellulose, microcrystalline
  • Maize starch
  • Croscarmellose sodium
  • Hypromellose
  • Magnesium stearate
  • Sodium laurilsulfate
  • Silica colloidal, anhydrous

Film coating

  • Hypromellose
  • Macrogols (8000)
  • Titanium dioxide (E171)
  • Talc
  • Ferric oxide red (E172)

Oral suspension

  • Microcrystalline cellulose (E460)
  • Carmellose sodium (E466)
  • Hydroxyethylcellulose
  • Citric acid, anhydrous (E330)
  • Simeticone emulsion, 30% containing benzoic acid, cyclotetrasiloxane, dimethicone, glycol stearate and glyceryl distearate, methylcellulose, PEG40 stearate (polyethylene glycol stearate), polysorbate 65, silica gel, sorbic acid, sulphuric acid and water.
  • Poloxamer 188
  • Methyl parahydroxybenzoate (E218)
  • Propyl parahydroxybenzoate (E216)
  • Propylene glycol (E1520).
  • Potassium sorbate (E202)
  • Sorbitol (E420), liquid (noncrystallising)
  • Orange flavour
  • Water

Incompatibilities

Not applicable.

Shelf Life

Film Coated Tablet

4 years.

Oral Suspension

3 years.

After first opening: 90 days.

Special Precautions for Storage

Film Coated Tablet

Do not store above 30°C.

Oral Suspension

This medicinal product does not require any special storage conditions. For storage conditions after first opening of the medicinal product, see Shelf life

Nature and Contents of Container

Film Coated Tablets

  • 100 mg: Aluminium/aluminium blisters, packs of 10, 30, 50, 60 and 100 filmcoated tablets.
  • 200mg: Aluminium/aluminium blisters, packs of 10, 30, 50, 60 and 100 filmcoated tablets.
  • 400 mg: Aluminium/aluminium blisters, packs of 10, 30, 50, 60, 100 and 200 filmcoated tablets.

Not all pack sizes may be marketed.

Oral Suspension

  • Orientedpolyethylene terephthalate (oPET) bottle with a childresistant polypropylene (PP) closure; each bottle contains 460 ml of suspension in an outer cardboard carton.
  • Each carton contains one bottle, two identical calibrated oral dosing syringes and a pressinbottle adapter (PIBA). The oral dosing syringes are graduated in 0.5 ml increments.

Special Precautions for Disposal and Other Handling

Film Coated Tablets

No special requirements.

Oral Suspension

Preparation: The pressinbottle adapter (PIBA) which is supplied in the product carton should be inserted firmly into the neck of the bottle before use and remain in place for the duration of the usage of the bottle. The dosing syringe should be inserted into the PIBA and the dose withdrawn from the inverted bottle. The cap should be replaced after each use. The cap fits properly when the PIBA is in place.

No special requirements for disposal.

Marketing Authorisation Holder

Eisai Limited, Mosquito Way, Hatfield, Hertfordshire, AL10 9SN, UK

Marketing Authorisation Number(s)

  • 100 mg 10 filmcoated tablets: EU/1/06/378/001
  • 100 mg 30 filmcoated tablets: EU/1/06/378/002
  • 100 mg 50 filmcoated tablets: EU/1/06/378/003
  • 100 mg 60 filmcoated tablets: EU/1/06/378/004
  • 100 mg 100 filmcoated tablets: EU/1/06/378/005
  • 200 mg 10 filmcoated tablets: EU/1/06/378/006
  • 200 mg 30 filmcoated tablets: EU/1/06/378/007
  • 200 mg 50 filmcoated tablets: EU/1/06/378/008
  • 200 mg 60 filmcoated tablets: EU/1/06/378/009
  • 200 mg 100 filmcoated tablets: EU/1/06/378/010
  • 400 mg 10 filmcoated tablets: EU/1/06/378/011
  • 400 mg 30 filmcoated tablets: EU/1/06/378/012
  • 400 mg 50 filmcoated tablets: EU/1/06/378/013
  • 400 mg 60 filmcoated tablets: EU/1/06/378/014
  • 400 mg 100 filmcoated tablets: EU/1/06/378/015
  • 400 mg 200 filmcoated tablets: EU/1/06/378/016
  • 40 mg/ml Oral suspension: EU/1/06/378/017

Date of First Authorisation/renewal of the Authorisation

Date of first authorisation: 16 January 2007

Date of latest renewal: 16 January 2012

Date of Revision of the Text

28 June 2013

Detailed information on this product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

Legal Category

POM Medicinal product subject to medical prescription

Company Contact Details

Eisai Ltd
http://www.eisai.co.uk

Address
European Knowledge Centre, Mosquito Way, Hatfield,
Hertfordshire, AL10 9SN

Telephone
+44 (0)845 676 1400

Fax
+44 (0)845 676 1486

Out of Hours Telephone
+44 (0)845 676 1400

Medical Information email
Lmedinfo@eisai.net