Ruzexin 150 ,300 & 600 150mg, 300 mg & 600 mg FC tablet

RUZEXIN is indicated for the treatment of partial seizures with or without secondary generalised seizures and generalised tonic-clonic seizures, in adults and in children aged 1 month and above. RUZEXIN may be used as monotherapy or adjunctive therapy in adults and in children of 1 month of age and above.

Posology
RUZEXIN is suitable for use either as monotherapy or in combination with other anti-epileptic medicines. In mono- and adjunctive therapy, treatment with RUZEXIN is initiated with a clinically effective dose given in two divided doses. The dose may be increased depending on the clinical response of the patient. When other antiepileptic medicines (AEMPs) are replaced by RUZEXIN, the dose of the concomitant AEMP(s) should be reduced gradually on initiation of RUZEXIN therapy. In adjunctive therapy, as the total antiepileptic medicines load of the patient is increased, the dose of concomitant AEMP(s) may need to be reduced and/or the RUZEXIN dose increased more slowly (see section 4.5).

Therapeutic drug monitoring
The therapeutic effect of oxcarbazepine is primarily exerted through the active metabolite 10-monohydroxy derivative (MHD) of oxcarbazepine (see section 5). Plasma level monitoring of oxcarbazepine or MHD is not routinely warranted. However, plasma level monitoring of MHD may be considered during RUZEXIN therapy in order to rule out noncompliance, or in situations where an alteration in MHD clearance is to be expected, including:
u2022 changes in renal function (see section 4.2)
u2022 pregnancy (see section 4.6)
u2022 concomitant use of liver enzyme-inducing medicines (see section 4.5)
If any of these situations apply, the dose of RUZEXIN may be adjusted (based on plasma levels measured 2 - 4 hours post dose) to maintain peak MHD plasma levels < 35 mg/L.

Adults:
Monotherapy and adjunctive therapy:
Initial dose
RUZEXIN should be initiated with a dose of 600 mg/day (8 - 10 mg/kg/day) given in 2 divided doses.
Maintenance dose
Good therapeutic effects are seen at doses between 600 mg/day and 2400 mg/day. If clinically indicated, the dose may be increased by a maximum of 600 mg/day increments at approximately weekly intervals from the starting dose to achieve the desired clinical response.
Maximum recommended dose
In a controlled hospital setting, dose increases up to 2400 mg/day have been achieved over 48 hours. Most adult patients are controlled on dosages of 900-1200 mg/day. Daily doses from 600 to 2400 mg/day have been shown to be effective in a controlled adjunctive therapy, although most patients were not able to tolerate the 2400 mg/day dose without reduction of concomitant anti-epileptic medicines, mainly because of CNS-related adverse events. Daily doses above 2400 mg/day have not been studied systematically in clinical trials.

Special populations
Elderly (65 years or above):
Dosages in the elderly may need to be reduced based on decreased renal function. Close monitoring of sodium levels is required in patients at risk of hyponatremia (see section 4.4).
Patients with hepatic impairment:
No dosage adjustment is required for patients with mild to moderate hepatic impairment. RUZEXIN has not been studied in patients with severe hepatic impairment, therefore, caution should be exercised when dosing severely impaired patients (see section 5.2).
Patients with renal impairment:
In patients with impaired renal function (creatinine clearance less than 30 mL/min) RUZEXIN therapy should be initiated at half the usual starting dose (300 mg/day) and increased slowly to achieve the desired clinical response (see section 5.2).
Paediatric population
Children:
Initial dose
In mono- and adjunctive therapy, RUZEXIN should be initiated with a dose of 8 - 10 mg/kg/day given in 2 divided doses.
Maintenance dose
The target maintenance dose of RUZEXIN for adjunctive therapy is 30 - 46 mg/kg/day and should be achieved over two weeks. In an adjunctive therapy in paediatric patients (aged 3 to 17 years), in which the intention was to reach a target daily dose of 46 mg/kg/day, the median daily dose was 31 mg/kg/day with a range of 6 to 51 mg/kg/day. In an adjunctive therapy in paediatric patients (aged 1 month to less than 4 years) in which the intention was to reach a target daily dose of 60 mg/kg/day, 56 % of patients reached a final dose of at least 55 mg/kg/day. If clinically indicated, the dose may be increased by a maximum of 10 mg/kg/day increments at approximately weekly intervals from the starting dose to a maximum daily dose of 60 mg/kg/day, to achieve the desired clinical response.
Effect of weight adjusted MHD clearance on paediatric dosage
Under adjunctive therapy and monotherapy, when normalised by body weight, apparent clearance (L/hr/kg) decreased with age such that children 1 month to less than 4 years of age may require twice the RUZEXIN dose per body weight compared to adults; and children 4 to 12 years of age may require a 50 % higher oxcarbazepine dose per body weight compared to adults (see section 5.2). For children 1 month to less than 4 years of age, the influence of enzyme-inducing antiepileptic medicines on their weight-normalised apparent clearance appeared higher compared to older children.
Effect of concomitant enzyme-inducing antiepileptic drugs on paediatric dosage
For children 1 month to less than 4 years of age, about 60 % higher RUZEXIN dose per body weight may be required for adjunctive therapy on enzyme-inducing antiepileptic medicines relative to monotherapy or adjunctive therapy with non-enzyme-inducing antiepileptic medicines. For older children on enzyme-inducing antiepileptic medicines, only a slightly higher dose per body weight may be required than their counterparts on monotherapy.
RUZEXIN has not been studied in controlled clinical trials in children below 1 month of age.
Method of administration
For oral use. The dosing recommendations above apply to all patients, in the absence of impaired renal function (see section 5.2). Drug plasma level monitoring is not necessary to optimize RUZEXIN therapy. The tablets are scored and can be broken in two halves in order to make it easier for the patients to swallow the tablet. If they are unable to swallow tablets an oral suspension must be used. RUZEXIN can be taken with or without food.

Known hypersensitivity to the active substance, oxcarbazepine, eslicarbazepine or to any of the excipients listed in section 6.1.

Hypersensitivity
Class I (immediate) hypersensitivity reactions including rash, pruritus, urticaria, angioedema and reports of anaphylaxis have been received in the post-marketing period. Cases of anaphylaxis and angioedema involving the larynx, glottis, lips and eyelids have been reported in patients after taking the first or subsequent doses of RUZEXIN. If a patient develops these reactions after treatment with RUZEXIN, the medicine should be discontinued, and an alternative treatment started.
Patients who have exhibited hypersensitivity reactions to carbamazepine should be informed that approximately 25-30 % of these patients may experience hypersensitivity reactions (e.g. severe skin reactions) with RUZEXIN (see section 4.8). Hypersensitivity reactions, including multi-organ hypersensitivity reactions, may also occur in patients without a history of hypersensitivity to carbamazepine. Such reactions can affect the skin, liver, blood and lymphatic system or other organs, either individually or together in the context of a systemic reaction (see section 4.8). In general, if signs and symptoms suggestive of hypersensitivity reactions occur, RUZEXIN should be withdrawn immediately.
Dermatological effects
Serious dermatological reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and erythema multiforme, have been reported very rarely in association with the use of RUZEXIN. Patients with serious dermatological reactions may require hospitalisation, as these conditions may be life-threatening and very rarely be fatal. RUZEXIN associated cases occurred in both children and adults. The median time to onset was 19 days. Several isolated cases of recurrence of the serious skin reaction when rechallenged with RUZEXIN were reported. Should a patient develop a skin reaction with RUZEXIN, consideration should be given to discontinuing RUZEXIN and prescribing another anti-epileptic medicine. Patients should be made aware of early toxic signs of the above-mentioned reactions, e.g., fever, rash, lesions in the mouth, bruising, purpura. They should be advised to contact their doctor immediately if such a reaction appears. RUZEXIN should not be restarted in patients who discontinued treatment due to a hypersensitivity reaction (see section 4.3).
Limitation of genetic screening
Genetic screening results must never substitute appropriate clinical vigilance and, patient management. Many Asian patients positive for HLA-B*1502 and treated with RUZEXIN will not develop SJS/TEN and patients negative for HLA-B*1502 of any ethnicity can still develop SJS/TEN. The same is true for HLA-A*3101 with respect to risk of SJS, TEN, DRESS, AGEP or maculopapular rash. The development of these severe cutaneous adverse reactions and its related morbidity due to other possible factors such as AED dose, compliance, concomitant medications, co-morbidities, and the level of dermatologic monitoring have not been studied.
Information for healthcare professionals
If testing for the presence of the HLA-B*1502 allele is performed, high-resolution u201cHLA -B*1502 genotypingu201d is recommended. The test is positive if either one or two HLA -B*1502 alleles are detected, and negative if no HLA-B*1502 alleles are detected. Similarly, if testing for the presence of the HLA- A*3101 allele is performed, high resolution u201cHLA - A*3101 genotypingu201d is recommended. The test is positive if either one or two HLA-A*3101 alleles are detected, and negative if no HLA- A*3101 alleles are detected.
Risk of seizure aggravation
Risk of seizure aggravation has been reported with RUZEXIN. The risk of seizure aggravation is seen especially in children but may also occur in adults. In case of seizure aggravation, RUZEXIN should be discontinued.
Hyponatraemia
Serum sodium levels below 125 mmoL/L, usually asymptomatic and not requiring adjustment of therapy, have been observed in up to 2,7 % of RUZEXIN treated patients. Experience shows that serum sodium levels returned towards normal when the RUZEXIN dosage was reduced, discontinued or the patient was treated conservatively (e.g., restricted fluid intake). In patients with pre-existing renal conditions associated with low sodium levels (e.g., inappropriate ADH secretion like syndrome) or in patients treated concomitantly with sodium-lowering medicines (e.g., diuretics, desmopressin) as well as NSAIDs (e.g., indomethacin), serum sodium levels should be measured prior to initiating therapy. Thereafter, serum sodium levels should be measured after approximately two weeks and then at monthly intervals for the first three months during therapy, or according to clinical need. These risk factors may apply especially to elderly patients. For patients on RUZEXIN therapy when starting on sodium-lowering medicines, the same approach for sodium checks should be followed. In general, if clinical symptoms suggestive of hyponatraemia occur on RUZEXIN therapy (see section 4.8), serum sodium measurement may be considered. Other patients may have serum sodium levels assessed as part of their routine laboratory studies. All patients with cardiac insufficiency and secondary heart failure should have regular weight measurements to determine occurrence of fluid retention. In case of fluid retention or worsening of the cardiac condition, serum sodium levels should be checked. If hyponatraemia is observed, water restriction is an important counter-measurement. As oxcarbazepine may, very rarely, lead to impairment of cardiac conduction, patients with pre-existing conduction disturbances (e.g. atrioventricular-block, dysrhythmia) should be followed carefully.
Bone marrow depression
If during treatment, low or decreased white blood cell or platelet counts are observed, the complete blood count and the patient should be monitored closely. RUZEXIN should be discontinued if any evidence of significant bone-marrow depression appears.
Hypothyroidism
Hypothyroidism is an adverse reaction (with u201cless frequentu201d frequency, see section 4.8) of oxcarbazepine. Considering the importance of thyroid hormones in children's development after birth, thyroid function monitoring is recommended in the paediatric age group while on RUZEXIN therapy.
Hepatic function
Cases of hepatitis have been reported, which in most cases resolved favourably. When a hepatic event is suspected, liver function should be evaluated and discontinuation of RUZEXIN should be considered. Caution should be exercised when treating patients with severe hepatic impairment (see sections 4.2 and 5.2).
Renal function
In patients with impaired renal function (creatinine clearance less than 30 mL/min), caution should be exercised during RUZEXIN treatment especially with regard to the starting dose and up titration of the dose. Plasma level monitoring of MHD may be considered (see sections 4.2 and 5.2).
Haematological effects
Agranulocytosis, aplastic anaemia and pancytopenia have been seen in patients treated with RUZEXIN during post-marketing experience (see section 4.8). Discontinuation of the medicines should be considered if any evidence of significant bone marrow depression develops.
Suicidal ideation and behaviour
Suicidal ideation and behaviour have been reported in patients treated with antiepileptic medicines in several indications. A meta-analysis of randomised placebo controlled trials of antiepileptic medicines 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 oxcarbazepine. 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.
Hormonal contraceptives
Female patients of childbearing age should be warned that the concurrent use of RUZEXIN with hormonal contraceptives may render this type of contraceptive ineffective (see section 4.5). Additional non-hormonal forms of contraception are recommended when using RUZEXIN.
Alcohol
Caution should be exercised if alcohol is taken in combination with RUZEXIN therapy, due to a possible additive sedative effect.
Withdrawal
As with all antiepileptic medicines, RUZEXIN should be withdrawn gradually to minimise the potential of increased seizure frequency. If RUZEXIN has to be discontinued abruptly, e.g. owing to severe adverse reactions, the change-over to another anti-epileptic preparation should be effected under cover of suitable medication (e.g. diazepam i.v., rectal; phenytoin i.v.) and under close supervision. RUZEXIN has a low enzyme-inducing potential. If, in patients on adjunctive therapy, carbamazepine or other anti-epileptics with enzyme-inducing properties are withdrawn and replaced by RUZEXIN, serum concentrations of the concurrent anti-epileptic medicine should be monitored to avoid possible toxicity; it may be necessary to reduce the dosage of the anti-epileptic co-medication (see section 4.5).

Enzyme induction
Oxcarbazepine and its pharmacologically active metabolite (the monohydroxy derivative, MHD) are weak inducers in vitro and in vivo of the cytochrome P450 enzymes CYP3A4 and CYP3A5 responsible for the metabolism of a very large number of medicines, for example, immunosuppressants (e.g. ciclosporin, tacrolimus), oral contraceptives (see below), and some other antiepileptic medicines (e.g. carbamazepine) resulting in a lower plasma concentration of these medicines (see table below summarising results with other antiepileptic medicines). In vitro, oxcarbazepine and MHD are weak inducers of UDP-glucuronyl transferases (effects on specific enzymes in this family are not known). Therefore, in vivo oxcarbazepine and MHD may have a small inducing effect on the metabolism of medicines which are mainly eliminated by conjugation through the UDP-glucuronyl transferases. When initiating treatment with RUZEXIN or changing the dose, it may take 2 to 3 weeks to reach the new level of induction. In case of discontinuation of RUZEXIN therapy, a dose reduction of the concomitant medications may be necessary and should be decided upon by clinical and/or plasma level monitoring.
The induction is likely to gradually decrease over 2 to 3 weeks after discontinuation.
Hormonal contraceptives:
RUZEXIN was shown to have an influence on the two components, ethinylestradiol (EE) and (levonorgestrel LNG), of an oral contraceptive. The mean AUC values of EE and LNG were decreased by 48-52 % and 32-52 % respectively. Therefore, concurrent use of RUZEXIN with hormonal contraceptives may render these contraceptives ineffective (see section 4.4). Another reliable contraceptive method should be used.
Enzyme inhibition
Oxcarbazepine and MHD inhibit CYP2C19. Therefore, interactions could arise when co-administering high doses of RUZEXIN with medicines that are mainly metabolised by CYP2C19 (e.g. phenytoin). Phenytoin plasma levels increased by up to 40 % when RUZEXIN was given at doses above 1,200 mg/day (see table below summarizing results with other anticonvulsants). In this case, a reduction of co-administered phenytoin may be required.
Antiepileptic and enzyme inducing medicines
Potential interactions between RUZEXIN and other antiepileptic medicines were assessed in clinical studies. The effect of these interactions on mean AUCs and C min are summarised in the following table.
Summary of antiepileptic medicinal product interactions with RUZEXIN
Antiepileptic medicine (AEMP) Influence of RUZEXIN on antiepileptic medicine (AEMP) Influence of antiepileptic medicine (AEMP) on MHD
Co-administered Concentration Concentration
Carbamazepine 0 - 22 % decrease (30 % increase of carbamazepine-epoxide) 40 % decrease
Clobazam Not studied No influence
Felbamate Not studied No influence
Lamotrigine No influence No influence
Phenobarbitone 14 - 15 % increase 30 - 31 % decrease
Phenytoin 0 - 40 % increase 29 - 35 % decrease
Valproic acid No influence 0 u2013 18 % decrease
Strong inducers of cytochrome P450 enzymes and/or UGT (i.e. rifampicin, carbamazepine, phenytoin and phenobarbitone) have been shown to decrease the plasma/serum levels of MHD (29-49 %) in adults; in children 4 to 12 years of age, MHD clearance increased by approximately 35% when given one of the three enzyme-inducing antiepileptic medicines compared to monotherapy. Concomitant therapy of RUZEXIN and lamotrigine has been associated with an increased risk of adverse events (nausea, somnolence, dizziness and headache). When one or several antiepileptic medicines are concurrently administered with RUZEXIN, a careful dose adjustment and/or plasma level monitoring may be considered on a case by case basis, notably in paediatric patients treated concomitantly with lamotrigine. No auto induction has been observed with RUZEXIN.

Women of childbearing potential and contraceptive measures
RUZEXIN may result in a failure of the therapeutic effect of oral contraceptive medicines containing ethinylestradiol (EE) and levonorgestrel (LNG) (see sections 4.4 and 4.5). Women of child bearing potential should be advised to use highly effective contraception (preferably non-hormonal; e.g. intrauterine implants) while on treatment with RUZEXIN.
Pregnancy
Data on a limited number of pregnancies indicate that RUZEXIN may cause serious birth defects (e.g. cleft palate) when administered during pregnancy. In animal studies, increased embryo mortality, delayed growth and malformations were observed. Taking these data into consideration:
u2022 If women receiving RUZEXIN become pregnant, plan to become pregnant or if the need to initiate treatment with RUZEXIN arises during pregnancy, the medicinesu2019 potential benefits must be carefully weighed against the potential risk of foetal malformations, (e.g., cleft palate). This is particularly important during the first three months of pregnancy.
u2022 Minimum effective doses should be given, and monotherapy whenever possible should be preferred at least during the first three months of pregnancy in women of childbearing age.
u2022 Patients should be counselled regarding the possibility of an increased risk of malformations and given the opportunity of antenatal screening.
u2022 During pregnancy, antiepileptic treatment must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.
Monitoring and prevention:
Antiepileptic medicines such as RUZEXIN may contribute to folic acid deficiency, a possible contributory cause of foetal abnormality. Folic acid supplementation is recommended before and during pregnancy. Due to physiological changes during pregnancy, plasma levels of the active metabolite of oxcarbazepine, the 10-monohydroxy derivative (MHD), may gradually decrease throughout pregnancy. It is recommended that clinical response should be monitored carefully in women receiving RUZEXIN treatment during pregnancy and determination of changes in MHD plasma concentrations should be considered to ensure that adequate seizure control is maintained throughout pregnancy. Determination of changes in MHD plasma concentrations should be considered. If dosages have been increased during pregnancy, postpartum MHD plasma levels may also be considered for monitoring.
In the newborn child:
Bleeding disorders in the newborn caused by antiepileptic medicines have been reported. As a precaution, vitamin K1 should be administered as a preventive measure in the last few weeks of pregnancy and to the newborn.
Oxcarbazepine as contained in RUZEXIN and its active metabolite (MHD) cross the placenta. Neonatal and maternal plasma MHD concentrations were similar in one case.
Breastfeeding
Oxcarbazepine as contained in RUZEXIN and its active metabolite (MHD) are excreted in breast milk. A milk-to-plasma concentration ratio of 0,5 was found for both. The effects on the infant exposed to RUZEXIN by this route are not known. Therefore, RUZEXIN is not recommended to be used during breastfeeding.
Fertility
There are no human data on fertility. In rats, fertility in both sexes was unaffected by oxcarbazepine or MHD at oral doses up to 150 and 450 mg/kg/day, respectively. However, disruption of oestrous cyclicity and reduced numbers of corpora lutea, implantations and live embryos were observed in female animals at the highest dose of MHD.

RUZEXIN has moderate influence on the ability to drive and use machines. Adverse reactions such as dizziness, somnolence, ataxia, diplopia, blurred vision, visual disturbances, hyponatremia and depressed level of consciousness were reported with RUZEXIN (for complete list of ADRs see section 4.8), especially at the start of treatment or in connection with dose adjustments (more frequently during the up titration phase). Patients should therefore exercise due caution when driving a vehicle or operating machinery.

SYSTEM ORGAN CLASS FREQUENCY ADVERSE REACTION
Blood and lymphatic system disorders Less frequent Leucopenia, bone marrow depression, aplastic anemia, agranulocytosis, pancytopenia, neutropenia, thrombocytopenia
Immune system disorders Less frequent Anaphylactic reactions, hypersensitivity #
Endocrine disorders Frequent Weight increased Less frequent Hypothyroidism
Metabolism and nutrition disorders Frequent Hyponatraemia u2020 Less frequent Inappropriate ADH secretion like syndrome with signs and symptoms of lethargy, nausea, dizziness, decrease in serum (blood) osmolality, vomiting, headache, confusional state or other neurological signs and symptoms, folic acid deficiency
Psychiatric disorders Frequent Agitation (e.g. nervousness), affect lability, confusional state, depression, apathy
Nervous system disorders Frequent Somnolence, headache, dizziness, ataxia, tremor, nystagmus, disturbance in attention, amnesia, Speech disorders (including dysarthria); more frequent during up titration of RUZEXIN dose
Eye disorders Frequent Diplopia, vision blurred, visual disturbance
Ear and labyrinth disorders Frequent Vertigo
Cardiac disorders Less frequent Atrioventricular block, dysrhythmia
Vascular disorders Less frequent Hypertension
Gastrointestinal disorders Frequent Vomiting, nausea, diarrhoea, abdominal pain, constipation Less frequent Pancreatitis and/or lipase and/or amylase increase
Hepato-biliary disorders Less frequent Hepatitis
Skin and subcutaneous tissue disorders Frequent Rash, alopecia, acne Less frequent Urticaria, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), Acute Generalised Exanthematous Pustulosis (AGEP), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), angioedema, erythema multiforme (see section 4.4)
Musculoskeletal, connective tissue and bone disorders Less frequent There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with RUZEXIN. The mechanism by which RUZEXIN affects bone metabolism has not been identified, systemic lupus erythematosus
General disorders and administration site conditions Frequent Fatigue, asthenia
Investigations Less frequent Hepatic enzymes increased, blood alkaline phosphatase increased, decrease in T4 (with unclear clinical significance)
Injury, poisoning and procedural complications Less frequent Fall
Description of selected adverse reactions
# Hypersensitivity (including multi-organ hypersensitivity) characterised by features such as rash, fever. Other organs or systems may be affected such as blood and lymphatic system (e.g. eosinophilia, thrombocytopenia, leucopenia, lymphadenopathy, splenomegaly), liver (e.g. hepatitis, abnormal liver function tests), muscles and joints (e.g. joint swelling, myalgia, arthralgia), nervous system (e.g. hepatic encephalopathy), kidneys (e.g. renal failure, nephritis interstitial, proteinuria), lungs (e.g. pulmonary oedema, asthma, bronchospasms, interstitial lung disease, dyspnoea), angioedema.
u2020 Serum sodium levels below 125 mmol/l have been observed in up to 2,7 % of RUZEXIN treated patients with frequency common (see section 4.4). In most cases, the hyponatraemia is asymptomatic and does not require adjustment of therapy. Less frequently, the hyponatraemia is associated with signs and symptoms such as seizures, encephalopathy, depressed level of consciousness, confusion, (see also nervous system disorders for further undesirable effects), vision disorders (e.g. blurred vision), hypothyroidism, vomiting, and nausea. Low serum sodium levels generally occurred during the first 3 months of treatment with RUZEXIN, although there were patients who first developed a serum sodium level <125 mmoL/more than 1 year after initiation of therapy (see section 4.4).
Adverse drug reactions from spontaneous reports and literature cases (frequency not known)
The following adverse drug reactions have been derived from post-marketing experience with oxcarbazepine via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorised as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness.
Immune system disorders: Drug Rash with Eosinophilia and Systemic Symptoms (DRESS).
Skin and subcutaneous tissue disorders: Acute Generalised Exanthematous Pustulosis (AGEP).
Musculoskeletal, connective tissue and bone disorders: There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with RUZEXIN. The mechanism by which oxcarbazepine affects bone metabolism has not been identified.
Paediatric population
In general, the safety profile in children was similar to that observed in the adult population (see section 5.1).

Symptoms
Symptoms of overdose include somnolence, dizziness, nausea, vomiting, hyperkinesia, hyponatraemia, ataxia and nystagmus.
Management
There is no specific antidote. Symptomatic and supportive treatment should be administered as appropriate. Removal of the medicine by inactivation by administering activated charcoal should be considered.