Oxcarbazepine


Generic Medicine Info
Indications and Dosage
Oral
Partial seizures
Adult: As monotherapy or adjunctive therapy: As conventional tab or oral susp: Initially, 600 mg daily in 2 divided doses; may be increased in Max increments of 600 mg daily at approx weekly intervals to achieve the desired clinical response. Usual maintenance dose: 600-2,400 mg daily. As extended-release tab: Initially, 600 mg once daily on an empty stomach (at least 1 hour before or 2 hours after meals); may be increased in increments of 600 mg daily at weekly intervals. Usual maintenance dose: 1,200-2,400 mg once daily.
Child: ≥6 years As monotherapy or adjunctive therapy: As conventional tab or oral susp: Initially, 8-10 mg/kg daily in 2 divided doses; may be increased in Max increments of 10 mg/kg daily at approx weekly intervals up to Max dose of 46 mg/kg daily. Usual maintenance dose (adjunctive therapy): 30-46 mg/kg daily. As extended-release tab: Initially, 8-10 mg/kg once daily on an empty stomach (at least 1 hour before or 2 hours after meals). Max: 600 mg daily during the 1st week of therapy. May increase dose at weekly intervals in increments of 8-10 mg/kg daily (Max dosage increment: 600 mg/dose) over 2-3 weeks to achieve desired maintenance dose. Dosage recommendations may vary among individual products or between countries (refer to specific product guidelines).
Elderly: As extended-release tab: Initially, 300 mg or 450 mg once daily on an empty stomach (at least 1 hour before or 2 hours after meals); may be increased in increments of 300-450 mg daily at weekly intervals to achieve the desired clinical response.

Oral
Generalised tonic-clonic seizures
Adult: As monotherapy or adjunctive therapy: As conventional tab or oral susp: Initially, 600 mg daily in 2 divided doses; may be increased in Max increments of 600 mg daily at approx weekly intervals to achieve the desired clinical response. Usual maintenance dose: 600-2,400 mg daily. Treatment recommendations may vary between countries (refer to specific product guidelines).
Special Patient Group
Pharmacogenomics:

Human leucocyte antigen (HLA) genetic variation, particularly the HLA-B*15:02 variant allele, is associated with a greater risk of serious cutaneous adverse reactions in response to aromatic anticonvulsants.

Patients with 1 or 2 copies of HLA-B*15:02, referred to as HLA-B*15:02 positive, may have an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) when treated with oxcarbazepine. The prevalence of HLA-B*15:02 allele ranges from 2-12% in Han Chinese populations, approx 8% in Thai populations, >15% in the Philippines and some Malaysian populations, up to approx 2% in Koreans, and approx 6% in Indians. The allele is quite rare in African Americans, several African populations, Middle Easterners, Caucasians, Hispanics/South Americans, and Japanese populations (<1%). Genetic testing may be considered to screen for the presence of HLA-B*15:02 variant allele before treatment initiation in patients with ancestry in genetically at-risk populations. However, genotyping must not substitute for clinical vigilance and patient management.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline recommends avoiding use of oxcarbazepine in HLA-B*15:02 positive patients who are oxcarbazepine-naive and considers the use of alternative aromatic anticonvulsants with weaker evidence linking SJS/TEN with HLA-B*15:02 allele. For patients who have previously used oxcarbazepine continuously for >3 months without the development of cutaneous reactions, CPIC recommends using oxcarbazepine with caution.

Moreover, the US Food and Drug Administration (FDA) drug label for oxcarbazepine states that the use of oxcarbazepine in HLA-B*15:02 positive patients must be avoided unless the benefits clearly outweigh the risks.
Renal Impairment
CrCl (mL/min) Dosage
<30 Initiate at half the usual starting dose (300 mg daily); may be increased slowly or in at least weekly intervals to achieve the desired clinical response.
Administration
May be taken with or without food.
Contraindications
Lactation.
Special Precautions
Patient with hypersensitivity reaction to carbamazepine, pre-existing renal conditions associated with low Na levels (e.g. inappropriate antidiuretic hormone secretion like syndrome), pre-existing conduction disturbances (e.g. atrioventricular block, arrhythmia), cardiac insufficiency, secondary heart failure. HLA-B*15:02 positive patients. Avoid abrupt withdrawal. Extended-release tab and conventional preparations are not bioequivalent, higher dosages may be needed when switching from conventional form to extended-release tab. Severe renal (CrCl <30 mL/min) and hepatic impairment. Children and elderly. Pregnancy.
Adverse Reactions
Significant: Immediate hypersensitivity reactions (e.g. rash, pruritus, urticaria, angioedema, anaphylaxis); seizure aggravation (particularly in children), hyponatraemia, hypothyroidism; agranulocytosis, leucopenia, pancytopenia, aplastic anaemia, thrombocytopenia, suicidal ideation and behaviour. Very rarely, impaired cardiac conduction, hepatitis.
Ear and labyrinth disorders: Vertigo.
Eye disorders: Nystagmus, visual disturbance, blurred vision, diplopia.
Gastrointestinal disorders: Nausea, vomiting, constipation, abdominal pain, diarrhoea.
General disorders and administration site conditions: Asthenia, fatigue.
Investigations: Weight increased.
Nervous system disorders: Headache, dizziness, somnolence, disturbance in attention, amnesia, speech disorders (including dysarthria), ataxia, tremor.
Psychiatric disorders: Apathy, depression, agitation, affect lability, confusional state.
Skin and subcutaneous tissue disorders: Alopecia, acne.
Potentially Fatal: Very rarely, serious dermatological reactions including SJS, TEN (Lyell's syndrome), erythema multiforme, drug reaction with eosinophilia and systemic symptoms (DRESS).
PO: Z (Insufficient data to conclude its safety and risk during pregnancy. Neonatal abstinence syndrome has been reported. Use only when benefits outweigh risks.)
Patient Counseling Information
This drug may cause dizziness, somnolence, lack of concentration, abnormal coordination, or visual disturbances; if affected, do not drive or operate machinery. Women of childbearing potential must use highly effective birth control methods during treatment. Consider using additional or other reliable contraceptive methods recommended by the doctor as hormonal contraceptives may be ineffective.
Monitoring Parameters
Consider screening for the presence of HLA-B*15:02 allele in patients at increased risk of developing oxcarbazepine-associated SJS/TEN before treatment initiation. Monitor serum Na levels for the 1st 3 months during therapy or based on clinical needs; seizure frequency; mental alertness and symptoms of CNS depression; signs and symptoms of skin or hypersensitivity reactions and suicidality. Obtain periodic thyroid function tests (particularly in children) and CBC.
Overdosage
Symptoms: Nausea, vomiting, somnolence, agitation, aggression, tremor, hypotension, hyponatraemia, confusional state, convulsion, abnormal coordination, depressed level of consciousness, dizziness, dyskinesia or hyperkinesia, diplopia, dyspnoea, QT prolongation, nystagmus, miosis, headache, blurred vision, decreased urine output, respiratory rate depression, coma. Management: Symptomatic and supportive treatment. May consider performing gastric lavage or administering activated charcoal.
Drug Interactions
May increase the risk of hyponatraemia with Na-lowering drugs (e.g. diuretics, desmopressin). May decrease the plasma concentrations and efficacy of hormonal contraceptives containing ethinylestradiol or levonorgestrel. May increase the plasma concentration of phenytoin. Strong CYP3A4 and/or uridine diphosphate glucuronosyltransferase (UGT) inducers (e.g. carbamazepine, phenytoin, phenobarbital, rifampicin) may decrease the plasma levels of the active metabolite of oxcarbazepine. May cause enhanced neurotoxicity with lithium.
Food Interaction
Additive sedative effect with alcohol.
Action
Description: Oxcarbazepine, a carbamazepine derivative, exerts its pharmacological activity primarily through its active metabolite, 10-monohydroxy derivative (MHD). The exact mechanism of action has not been defined; however, it is known that oxcarbazepine and MHD inhibit the voltage-sensitive Na channels, leading to the stabilisation of hyperexcited neural membranes, suppression of repetitive neuronal firing, and reduction of propagation of synaptic impulses. These actions are thought to be significant in preventing the spread of seizures in the brain. Additionally, increased K conductance and modulation of high-voltage activated Ca channels may contribute to the anticonvulsant effects of oxcarbazepine.
Pharmacokinetics:
Absorption: Completely absorbed from the gastrointestinal tract. Time to peak plasma concentration: MHD: 4.5 hours (tab); 6 hours (oral susp); 7 hours (extended-release tab).
Distribution: Widely distributed throughout the body (MHD). Crosses the placenta and enters breast milk. Volume of distribution: 49 L (MHD). Plasma protein binding: 67% (oxcarbazepine); approx 40% (MHD), mainly to albumin.
Metabolism: Rapidly and extensively metabolised in the liver by cytosolic enzymes into MHD (active); MHD is further metabolised via glucuronide conjugation; 4% of the dose is oxidised into inactive 10,11-dihydroxy derivative (DHD).
Excretion: Via urine (>95%, <1% as unchanged oxcarbazepine, 27% as unchanged MHD, 49% as MHD glucuronides, approx 3% as DHD, 13% as conjugates of oxcarbazepine and MHD); faeces (<4%). Elimination half-life: Conventional preparations: Approx 2 hours (oxcarbazepine); approx 9 hours (MHD). Extended-release tab: 7-11 hours (oxcarbazepine); 9-11 hours (MHD).
Chemical Structure

Chemical Structure Image
Oxcarbazepine

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 34312, Oxcarbazepine. https://pubchem.ncbi.nlm.nih.gov/compound/Oxcarbazepine. Accessed Oct. 27, 2022.

Storage
Store between 15-30°C. Protect the extended-release tab from light and moisture.
MIMS Class
Anticonvulsants
ATC Classification
N03AF02 - oxcarbazepine ; Belongs to the class of carboxamide derivatives antiepileptic.
References
Phillips E, Sukasem C, Whirl-Carillo M et al. Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clinical Pharmacology and Therapeutics. 2018;103(4):1-8. doi: 10.1002/cpt.1004. Accessed 07/09/2022

Annotation of FDA Label for Oxcarbazepine and HLA-B. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 07/09/2022.

Anon. HLA-B - Oxcarbazepine (Pharmacogenomics). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/09/2022.

Anon. Oxcarbazepine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/09/2022.

Buckingham R (ed). Oxcarbazepine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/09/2022.

Clinical Annotation for HLA-B*15:02:01; Oxcarbazepine; Stevens-Johnson Syndrome (Level 1A Toxicity). Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 07/09/2022.

Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clinical Pharmacogenetics Implementation Consortium (CPIC). https://cpicpgx.org. Accessed 07/09/2022.

Joint Formulary Committee. Oxcarbazepine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/09/2022.

Novartis New Zealand Limited. Trileptal Film Coated Tablets and Oral Suspension data sheet 02 September 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 05/09/2022.

Oxcarbazepine Suspension (Akorn). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/09/2022.

Oxcarbazepine Tablet (Supernus Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/09/2022.

Trileptal 150 mg Film-coated Tablets (Novartis Ireland Limited). MHRA. https://products.mhra.gov.uk. Accessed 05/09/2022.

Trileptal 60 mg/mL Oral Suspension (Novartis Ireland Limited). MHRA. https://products.mhra.gov.uk. Accessed 05/09/2022.

Trileptal Film-coated Tablets (Novartis Corporation [Malaysia] Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 05/09/2022.

Trileptal Tablet, Film Coated; Trileptal Suspension (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/09/2022.

Disclaimer: This information is independently developed by MIMS based on Oxcarbazepine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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