- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of oxcarbazepine
Epilepsy-partial seizures with/without secondary generalisation-adjunctive
Epilepsy-partial seizures with/without secondary generalisation-monotherapy
It is recommended that prescriptions for oxcarbazepine oral suspension be presented as millilitres and rounded to the nearest 0.5 ml.
Suggested starting dose 600 mg/day (8 to 10 mg/kg/day) given in 2 divided doses.
The dose may be increased, at weekly intervals, by a maximum of 600 mg/day increments until the desired response is achieved. Therapeutic responses are seen at doses between 600 mg/day and 2400 mg/day.
Evidence suggests 1200 mg/day is an effective dose, although 2400 mg/day has been shown to be effective in more refractory patients converted from other antiepileptic medicinal products to oxcarbazepine monotherapy.
Most patients on adjunctive therapy were not able to tolerate the 2400 mg/day dose without reduction of concurrent antiepileptic medicinal products.
In a controlled hospital setting, dose increases up to 2400 mg/day have been achieved over 48 hours.
Doses exceeding 2400 mg/day have not been studied.
Adjustment of the dose is recommended in the elderly with renal impairment.
(See Dosage; Adult)
Monotherapy and adjunctive therapy
6 to 18 years of age
Suggested starting dose 8 to 10 mg/kg/day in 2 divided doses (maximum dose of 600 mg/day).
If clinically indicated the dose may be increased, at weekly intervals, by a maximum of 10 mg/kg/day increments to a maximum dose of 46 mg/kg/day.
In adjunctive therapy, therapeutic effects were seen at a median maintenance dose of approximately 30 mg/kg/day.
Patients with Renal Impairment
Creatinine clearance less than 30 ml per minute
Initiate therapy at half the usual starting dose (300 mg/day) and increase at intervals not less than weekly to achieve the desired clinical response.
Dose escalation in patients with impaired renal function may require more careful observation.
Additional Dosage Information
The oral suspension and the tablets may be interchanged at equal doses.
When other antiepileptic medicinal products are replaced by oxcarbazepine, the dose of the concurrent antiepileptic agent should be reduced gradually on initiation of oxcarbazepine. In adjunctive therapy, as the total antiepileptic medicinal product load of the patient is increased, the dose of the concurrent antiepileptic medicinal product(s) may need to be reduced and/or the oxcarbazepine dose increased more slowly.
Children under 6 years
Precautions and Warnings
East Asian ancestry
Females of childbearing potential
Cardiac conduction defects
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment
Reduce dose in patients with creatinine clearance below 30ml/min
Advise ability to drive/operate machinery may be affected by side effects
Advise patient somnolence may affect ability to drive or operate machinery
Confirm HLA-B 1502 status in Han Chinese & Thai patients before initiating
Consider prescribing by manufacturer to ensure seizure control maintenance
Folic acid 5mg daily required pre-conception to end of 1st trimester
Oral solution contains alcohol
Oral solution contains parabens: Potential for delayed allergic reactions
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Never rechallenge treatment after a hypersensitivity reaction
Monitor patients with low serum sodium before and during treatment
Breastfeeding: Monitor infant for systemic effects of treating the mother
If hepatic impairment symptoms occur monitor LFT & consider discontinuation
Monitor ECG and serum potassium in patients with severe cardiac impairment
Monitor elderly for hyponatraemia if drowsy, confused, fitting
Monitor for signs of fluid retention
Monitor weight for fluid retention in patients with cardiac insufficiency
Refer women considering pregnancy for specialist advice and monitoring
Advise patient to report symptoms of allergic type hypersensitivity
Advise patient to seek medical advice if severe skin reaction occurs
Advise patients/carers to seek medical advice if suicidal intent develops
Consult Dr.at once if rash, sore throat, mouth ulcers, bruising,fever occur
Avoid abrupt withdrawal
Discontinue if evidence of significant bone marrow depression
Discontinue if hypersensitivity reactions occur
Discontinue if severe skin reaction occurs
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Female: Barrier or non-hormonal contraception advised during treatment
Neonate exposed in utero: Administer vitamin K at birth
Pregnancy: Administer vitamin K in the last few weeks of pregnancy
Antiepileptic drug hypersensitivity syndrome is a rare but potentially fatal syndrome associated with some antiepileptic drugs. Patients usually present with fever, rash, lymphadenopathy and other organ system involvement. Other possible symptoms include liver dysfunction, haematological, renal and pulmonary abnormalities, vasculitis and multi-organ failure. Class I (immediate) hypersensitivity reactions including rash, pruritis, angioderma and anaphylaxis involving the eyelids, larynx, glottis and lips have been observed. If signs or symptoms of hypersensitivity syndrome occur, the drug should be withdrawn immediately and expert advice sought.
Approximately 25 to 30% of patients who have exhibited hypersensitivity reaction to carbamazepine may experience severe hypersensitivity reactions to oxcarbazepine. However, hypersensitivity reactions can occur in patients without a history of hypersensitivity to carbamazepine.
Severe dermatological reactions
Severe dermatological reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome have been rarely reported during treatment with carbamazepine. These reactions usually appear within the first few months of treatment. The HLA-B*1502 allele has been strongly associated with risk of developing Stevens-Johnson syndrome. Genetic screening of patients who are of Han Chinese or Thai origin should be considered as the HLA-B*1502 allele is more prevalent in these populations (approximately 10%). If patient tests positive for this allele carbamazepine treatment should not be initiated unless there is no other therapeutic option.
Severe dermatological reactions have also been associated with the HLA-A*3101 allele in European and Japanese populations. There is currently there is insufficient data to support genetic testing for this allele, although if a patient is known to be positive for the allele, the use of carbamazepine may be considered if the benefits are thought to outweigh the risk.
Milder reactions (macular and maculopapular exanthema) may also occur and may dissipate upon dose reduction or continued treatment; these patients should be monitored closely for potential immediate withdrawal on worsening reaction.
Serum sodium levels below 125 mmol/l have been observed. This is usually asymptomatic and resolves when oxcarbazepine dosage is reduced, discontinued or the patient treated conservatively (e.g. restriction of fluid intake). Measure serum sodium levels before initiating therapy in patients with pre-existing renal conditions associated with low serum sodium or patients receiving concurrent sodium-lowering medicinal products (e.g. diuretics, desmopressin, NSAIDs). Thereafter, measure serum sodium after two weeks and then monthly for the first three months during therapy, or according to clinical need. These risk factors may apply especially to elderly patients. Similar considerations apply to patients already taking oxcarbazepine when starting sodium-lowering therapy.
All patients with cardiac insufficiency or secondary cardiac failure should have regular weight checks to determine the occurrence of fluid retention. In cases of fluid retention or worsening of the cardiac condition, check for hyponatraemia. If this is observed, water restriction is an important counter measure. Monitor patients with pre-existing cardiac conduction disturbances carefully as rarely, cardiac conduction impairment occurs.
Antiepileptic treatment is associated with a small increased risk of suicidal thoughts and behaviour, available data suggest that the increased risk applies to all antiepileptics and is seen as early as one week after starting treatment. Patients (and carers of patients) should be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment. They should be advised to seek medical advice if they develop such thoughts or behaviour, and should be referred for appropriate treatment if necessary.
The available evidence does not define whether the risk of suicidal thoughts and behaviour differs between antiepileptics. Patients should not stop or switch treatment on the basis of this information and without speaking to a healthcare professional.
Pregnancy and Lactation
Use oxcarbazepine with caution in pregnancy.
Careful re-evaluation of therapy should take place. Evaluate the benefits and risks of continuing anti-epileptic therapy throughout pregnancy. Adjusting or stopping any anti-epileptic medication during pregnancy should not be done without specialist advice, and the relative benefits and risks should be discussed carefully first. The risk of inadequate seizure control may be more detrimental to the foetus than the use of antiepileptic drugs. It has been shown that the prevalence of malformations in the offspring of women with epilepsy is two to three times higher than the approximately 3% in the general population. Whilst an increase has been noted with polytherapy the extent to which medications/the illness has contributed has not been elucidated. Routine monitoring of antiepileptic drugs is not recommended, but may be useful in cases where seizures have increased or are likely to, in order to plan the extent of dose adjustment needed. Oxcarbazepine and its active metabolite cross the placenta. There is insufficient evidence to assess the teratogenic potential of oxcarbazepine, however it is thought that oxcarbazepine may cause serious birth defects (e.g. cleft palate, neural tube defects and other minor craniofacial malformations) when administered during pregnancy. If women receiving the drug become pregnant, or need to receive oxcarbazepine while pregnant, the potential benefits must be carefully weighed against the potential risk of foetal malformations. This is particularly important during the first trimester. Oxcarbazepine has been found to be teratogenic in rats but not in rabbits. However, in fertility studies with the active metabolite, an oral dose of 2 times the maximum recommended human dose caused disruption of the oestrous cycle and a reduction of numbers of corpora lutea, implantations and live embryos. Patients should be advised of the increased risk of foetal malformations and provide the opportunity of antenatal screening. Minimum effective doses should be given and, in women of child bearing age, monotherapy should be used wherever possible. Vitamin K1 should be administered in the last few weeks of pregnancy and to the neonate to prevent bleeding disorders that have been reported to be cause by antiepileptic agents. The Clinical Knowledge Summaries recommend that folic acid 5 mg daily should be prescribed to all women with epilepsy who are taking antiepileptic drugs, prior to conception and continued until the 12th week of pregnancy. Schaefer (2007) recommends that if exposed to oxcarbazepine during pregnancy, the mother should undergo a detailed ultrasound in the second trimester, as well as an alpha-fetoprotein determination in the maternal serum around the sixteenth week. Oxcarbazepine may render hormonal contraceptives ineffective, therefore advise female patients of child bearing potential to use alternative methods of contraception. Data from a limited number of women indicate that plasma levels of the active metabolite of oxcarbazepine may gradually decrease throughout pregnancy. It is recommended that clinical response should be carefully monitored in women receiving oxcarbazepine treatment during pregnancy to ensure adequate seizure control is maintained. Determination of changes in metabolite concentrations should be considered. If dosages have been increased during pregnancy, postpartum metabolite levels may also be considered for monitoring.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Oxcarbazepine is contraindicated in breastfeeding.
Oxcarbazepine and its active metabolite are excreted in human breast milk. A milk-to-plasma concentration ratio of 0.5 was found for both oxcarbazepine and its metabolite. The effects on the nursing infant are unknown.
If oxcarbazepine is administered during breastfeeding, the infant should be monitored for drowsiness, adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants and when using a combination of anticonvulsants.
Limited information suggests that oxcarbazepine would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Abnormal liver function tests
Bone marrow depression
Decrease in blood thyroxine values
Decrease in bone mineral density
Elevated amylase levels
Elevated serum lipase
Increase in alkaline phosphatase
Increases in hepatic enzymes
Interstitial lung disease
Lability of affect
Systemic lupus erythematosus
Toxic epidermal necrolysis
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: April 2014
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on [March 19, 2014].
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Summary of Product Characteristics: Trileptal 150 mg, 300 mg & 600 mg Film-coated Tablets. Novartis Pharmaceuticals UK Ltd. Revised April 2013.
Summary of Product Characteristics: Trileptal 60 mg/ml Oral Suspension. Novartis Pharmaceuticals UK Ltd. Revised April 2013.
Summary of Product Characteristics: Oxcarbazepine 150 mg Film-coated tablets. Generics UK Ltd. Revised April 2011.
Summary of Product Characteristics: Oxcarbazepine 300 mg Film-coated tablets. Generics UK Ltd. Revised April 2011.
Summary of Product Characteristics: Oxcarbazepine 600 mg film-coated tablets. Generics UK Ltd. Revised April 2011.
MHRA Drug Safety Update December 2012
Available at: https://www.mhra.gov.uk
Last accessed: March 19, 2014
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
oxcarbazepine Last revised: September 07, 2013
Last accessed: March 19, 2014
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