Food and Drug Administration. Conventional (immediate-release) tablets and oral suspension: Monotherapy of partial seizures in adults and pediatric patients ≥4 years of age.Extended-release tablets: Adjunctive therapy (i.e., in combination with other anticonvulsants) of partial seizures in adults and pediatric patients ≥6 years of age.Has been used alone or in combination with other drugs (e.g., antipsychotic agents) for treatment and prevention of acute manic or mixed episodes in patients with bipolar disorderAmerican Psychiatric Association (APA) considers oxcarbazepine an alternative treatment option for patients who have had an inadequate response to first-line agents (e.g., lithium, valproate, antipsychotic agents [e.g., olanzapine]).Withdraw gradually to minimize the potential for increased seizure frequency and status epilepticus.Closely monitor for notable changes in behavior that could indicate emergence or worsening of suicidal thoughts or behavior or depression.Consider pharmacogenetic testing for the variant HLA-B*1502 allele in patients who may be at increased risk of oxcarbazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).Prior to initiating oxcarbazepine therapy, consider screening patients with ancestry in genetically at-risk populations for HLA-B*1502.The test is considered positive if 1 or 2 copies of HLA-B*1502 are detected and negative if no copies are detected.Do not initiate therapy in HLA-B*1502-positive patients unless benefits clearly outweigh risks.Because of limitations, HLA-B*1502 genotyping should never substitute for appropriate clinical vigilance and patient management.For additional information and guidance on how to interpret and apply results of HLA-B*1502 testing, consult the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for HLA genotype and use of carbamazepine and oxcarbazepine.Administer orally as conventional (immediate-release) tablets, oral suspension, or extended-release tablets.Conventional tablets and oral suspension can be used interchangeably on a mg-for-mg basis.Administer orally twice daily without regard to meals.Administer orally once daily on an empty stomach (i.e., at least 1 hour before or 2 hours after a meal).Swallow tablets whole with water or other liquid; do not cut, crush or chew.Administer orally twice daily without regard to meals.Shake suspension well immediately prior to administration.Measure and administer appropriate dose using oral dosing syringe supplied by manufacturer; dose may be added to a small glass of water or swallowed directly from the syringe.Children 4–16 years of age not currently receiving any anticonvulsant drug therapy: Initially, 8–10 mg/kg daily (administered as 4–5 mg/kg twice daily).Children 4–16 years of age being transferred from other anticonvulsant drug therapy to oxcarbazepine monotherapy: Initially, 8–10 mg/kg daily (administered as 4–5 mg/kg twice daily).Dosage adjustment is recommended in patients receiving concomitant therapy with enzyme-inducing drugs.Children 2 to <4 years of age: Initially, 8–10 mg/kg (generally not to exceed 600 mg) daily (administered as 4–5 mg/kg twice daily).Children 4–16 years of age: Initially, 8–10 mg/kg (not to exceed 600 mg) daily (administered as 4–5 mg/kg twice daily).Children ≥6 years of age: Initially, 8–10 mg/kg once daily (not to exceed 600 mg once daily for the first week).Patients not currently receiving any anticonvulsant drug therapy: Initially, 600 mg daily (administered as 300 mg twice daily).Patients being transferred from other anticonvulsant drug therapy to oxcarbazepine monotherapy: Initially, 600 mg daily (administered as 300 mg twice daily).Dosage adjustment is recommended in patients receiving adjunctive therapy with enzyme-inducing drugs.Initially, 600 mg daily (administered as 300 mg twice daily).Initially, 600 mg once daily for the first week; increase subsequent dosage by increments of 600 mg daily at weekly intervals to recommended dosage of 1.2–2.4 g once daily.Adjunctive therapy in children 2 to <4 years of age: Manufacturer of conventional preparations recommends maximum maintenance dosage of 60 mg/kg daily (administered as 30 mg/kg twice daily).Manufacturer of conventional preparations recommends maximum dosage of 2.4 g daily (administered as 1.2 g twice daily) when used as monotherapy in previously treated patients.Manufacturer of conventional preparations recommends maximum dosage of 1.2 g daily (administered as 600 mg twice daily) when used as adjunctive therapy.Manufacturer makes no specific dosage recommendations.Use immediate-release preparations (instead of extended-release preparations) in patients with end-stage renal disease on dialysis.Manufacturer of conventional oxcarbazepine preparations makes no specific dosage recommendations.Manufacturer of extended-release tablets recommends consideration of initial reduced dosage of 300 or 450 mg daily; increase dosage in increments of 300–450 mg daily at weekly intervals to achieve desired response.Known hypersensitivity to oxcarbazepine or any ingredient in the formulation, or to eslicarbazepine.Possible hyponatremia (serum sodium concentrations <125 mEq/L);Consider monitoring serum sodium concentrations, particularly in patients receiving other drugs known to decrease sodium concentrations (e.g., drugs associated with SIADH) or in those with symptoms of hyponatremia (e.g., nausea, malaise, headache, lethargy, confusion, obtundation, increase in seizure frequency or severity).Serious and sometimes fatal dermatologic reactions, including SJS and TEN, reported.Strong association demonstrated between presence of HLA-B*1502 (an inherited allelic variant of the HLA-B gene) and risk of developing SJS and TEN with carbamazepine, a closely related drug.HLA-B*1502 is found almost exclusively in patients with ancestry across broad areas of Asia (including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais), and largely absent in individuals not of Asian origin (e.g., Caucasians, African-Americans, Hispanics, Native Americans).Prior to initiating oxcarbazepine therapy, consider screening genetically at-risk populations for HLA-B*1502.Possibility of increased seizure frequency and status epilepticus following discontinuance of therapy.Possible neuropsychiatric effects including impaired cognitive or psychomotor performance (e.g., difficulties in concentrating, language, and speech); somnolence or fatigue; and coordination difficulties (e.g., ataxia, gait disturbances).Increased risk of suicidality (suicidal behavior or ideation) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.Balance risk of suicidality with risk of untreated illness.Pancytopenia, agranulocytosis, and leukopenia reported rarely.Plasma concentrations of the active metabolite of oxcarbazepine (MHD) may decrease during pregnancy.Monitor patients during pregnancy and throughout postpartum period.Risk of seizure exacerbation or new-onset primary generalized seizures, especially in children.Anaphylaxis and angioedema involving the larynx, glottis, lips, and eyelids reported rarely; sometimes fatal.Approximately 25–30% of patients with a history of carbamazepine hypersensitivity will develop hypersensitivity to oxcarbazepine.Patients with previous hypersensitivity to carbamazepine should be treated with oxcarbazepine only if potential benefits outweigh risks.Multi-organ hypersensitivity (also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) reported; can be fatal or life-threatening.If manifestations of multi-organ hypersensitivity occur, evaluate patient immediately.No adequate and well-controlled studies in pregnant women; however, the drug is closely related to carbamazepine, which has been associated with teratogenic effects in humans.Due to physiologic changes that occur during pregnancy, plasma concentrations of MHD (active metabolite) may gradually decrease during pregnancy; closely monitor patients for possible decreased seizure control during pregnancy and throughout postpartum period.North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 (for patients); registry information also available on the website Oxcarbazepine and its active MHD metabolite are distributed into milk.Safety and efficacy of conventional preparations as monotherapy of partial seizures not established in children <4 years of age.Safety and efficacy of conventional preparations as adjunctive therapy of partial seizures not established in children <2 years of age.Extended-release tablets not recommended in children <6 years of age because of administration difficulties and lack of studies in children <4 years of age.Risk of seizure aggravation may be higher in the pediatric population compared with adults.Clearance of MHD may be increased in younger children compared with adults; therefore, dosing requirements may be increased in pediatric patients.Systemic exposure to MHD may be increased (see Absorption: Special Populations, under Pharmacokinetics).Closely monitor serum sodium concentrations in geriatric patients at risk for hyponatremia.Pharmacokinetics do not appear to be affected by mild to moderate hepatic impairment.Principally eliminated renally; pharmacokinetics may be altered in patients with renal impairment.Conventional preparations: Dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, nystagmus, tremor, dyspepsia, abnormal gait.Extended-release tablets: Dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, asthenia, fatigue.CYP2C19 substrates: Potential increased plasma concentrations of the CYP2C19 substrate.CYP3A4 and CYP3A5 substrates: Potential decreased plasma concentrations of the CYP3A4 or CYP3A5 substrate.Potent CYP3A4 inducers: Potential decreased plasma concentrations of MHD.UGT inducers: Potential decreased plasma concentrations of MHD.Consider avoidance of other drugs associated with SJS and TEN in HLA-B*1502-positive patients when alternative therapies are available.Possible decreased plasma concentrations of dihydropyridine calcium-channel blocking agentsFelodipine: Systemic exposure of felodipine decreased by 28%Verapamil: Plasma concentrations of active metabolite of oxcarbazepine (MHD) decreased by 20%No substantial change in carbamazepine concentrations; plasma concentrations of MHD decreased by 40%Monitor plasma MHD concentrations during titration of oxcarbazepine; dosage adjustment of oxcarbazepine may be necessary when initiating, discontinuing, or modifying dosage of carbamazepineIn patients receiving oxcarbazepine extended-release tablets, consider increased initial dosage of 900 mg dailyIncreased metabolism of oral estrogen-progestin contraceptives; systemic exposures of estrogen and progestin components decreased by 48–52 and 32–52%, respectivelyPossible decreased contraceptive efficacy; women of childbearing potential should use additional nonhormonal methods of contraceptionPossible decreased plasma concentrations of cyclosporineNo substantial change in pharmacokinetics of either lamotrigine or MHDPlasma concentrations of phenobarbital increased by 14%;Monitor plasma MHD concentrations during titration of oxcarbazepine; dosage adjustment of oxcarbazepine may be necessary when initiating, discontinuing, or modifying dosage of phenobarbitalIn patients receiving oxcarbazepine extended-release tablets, consider increased initial dosage of 900 mg dailyPlasma phenytoin concentrations increased by up to 40% when administered concomitantly with oxcarbazepine dosages >1.2 g daily;Monitor plasma phenytoin concentrations when oxcarbazepine is titrated or dosage is adjusted; reduction of phenytoin dosage may be requiredMonitor plasma MHD concentrations during titration of oxcarbazepine; dosage adjustment of oxcarbazepine may be necessary when initiating, discontinuing, or modifying dosage of phenytoinIn patients receiving oxcarbazepine extended-release tablets, consider increased initial dosage of 900 mg dailyMonitor plasma MHD concentrations during titration of oxcarbazepine; dosage adjustment of oxcarbazepine may be necessary when initiating, discontinuing, or modifying dosage of rifampinNo substantial effect on valproic acid concentrations; concentrations of MHD decreased by 18%Oral bioavailabilities of conventional tablets and oral suspension appear to be similar.Conventional preparations: Peak plasma concentrations are attained in approximately 4.5 or 6 hours following twice-daily administration as conventional tablets or oral suspension, respectively.Extended-release tablets: Peak plasma concentrations of MHD are attained in 7 hours following once-daily administration.Conventional tablets: Food does not affect rate or extent of absorption.Oral suspension: Although not specifically evaluated, food is not expected to affect oral bioavailability.Extended-release tablets: Administration with a high-fat meal did not affect overall exposure to the active MHD metabolite, but increased peak plasma concentrations of MHD by about 60% and decreased time to peak plasma concentrations by about 2 hours.In geriatric patients >65 years of age, peak plasma concentrations and AUC of MHD may be 30–60% higher than values in younger adults.MHD exposure in children 2 to <4 years of age is approximately 50% of the exposure in adults when similar weight-adjusted dosages are given.Extensively metabolized in the liver by cytosolic enzymes to the MHD metabolite,Excreted in urine (>95%), mainly as metabolites, and in feces (<4%).Oxcarbazepine: Approximately 2 hours following administration of conventional preparations.MHD: Approximately 9 hours following administration of conventional preparations.In patients with mild to moderate hepatic impairment, pharmacokinetics of oxcarbazepine and MHD unaffected based on studies with immediate-release oxcarbazepine.In children 2 to <4 years of age, weight-adjusted clearance of MHD is approximately 80% higher than that of adults.In children 4–12 years of age, weight-adjusted clearance of MHD is approximately 40% higher than that of adults.In children ≥13 years of age, weight-adjusted MHD clearance expected to be similar to that of adults.Tight container at 25°C (may be exposed to 15–30°C).Tight, light-resistant container at 25°C (may be exposed to 15–30°C); protect from light and moisture,Original container at 25°C (may be exposed to 15–30°C).Exact mechanism of action is unknown; may prevent spread of epileptic seizures by stabilizing excitatory neuronal membranes, inhibiting repetitive neuronal firing, and decreasing propagation of synaptic impulses (by blocking voltage-sensitive sodium channels).Increased potassium conductance and modulation of high-voltage activated calcium channels also may contribute to anticonvulsant activity.Protects against electrically induced tonic extension seizures and, to a lesser degree, chemically induced clonic seizures; may abolish or reduce frequency of chronically recurring focal seizures.Importance of advising patients to read the patient information (medication guide).Risk of hypersensitivity reaction; patients who have had previous hypersensitivity reaction to carbamazepine at increased risk.Risk of dizziness and somnolence; avoid driving or operating machinery until effects on individual are known.Risk of suicidality (anticonvulsants may increase risk of suicidal thoughts or actions in about 1 in 500 people).Risk of hyponatremia; manifestations may include nausea, extreme drowsiness and/or fatigue, lack of energy, headache, confusion, or increase in seizure frequency or severity.Risk of hematologic effects; importance of advising patients to immediately report any manifestations suggestive of a blood disorder.Caution if alcohol is used concomitantly because additive sedative effects may occur.Importance of taking oxcarbazepine as prescribed and not abruptly discontinuing therapy.Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.Importance of advising patients of other important precautionary information.
A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy.
The regulation of serum sodium after replacing carbamazepine with oxcarbazepine. Scachter SC, Vazquez B, Fisher RS et al. 11. 12.
Inhibits repetitive neuronal firing, and decreased propagation of neuronal impulses.Monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children age 416.Hypersensitivity to oxcarbazepine; pregnancy (category C), lactation; children <4 y.Older adults; renal impairment; children <8 y; infertility, hyponatremia, SIADH, and drugs associated with SIADH as an adverse
Safety and efficacy of conventional preparations as monotherapy of partial seizures not established in children <4 years of age. Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partial epilepsy.
Adjunctive therapy with oxcarbazepine in children with partial seizure. * available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name3. 1 24. Emrich et al. 21. 20. Dam M, Ekberg R, Loyning Y et al. Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Oxcarbazepine: double-blind, randomized, placebo-control, monotherapy trial for partial seizures. 14. 1 12 French JA, Baroldi P, Brittain ST et al. 15. Barcs G, Walker EB, Elger CE et al. physical therapy implications Examination and Evaluation Monitor signs of allergic and hypersensitivity reactions, including pulmonary symptoms (tightness in the throat and chest, wheezing, cough, dyspnea) or skin reactions (rash, pruritus, urticaria). A double-blind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed, previously untreated epilepsy.
Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double-blind, clinical trial. Glauser TA, Nigro M, Sachdeo R et al. 1 24 Discontinue nursing or the drug.
9.
Headache, dizziness, somnolence, ataxia, nystagmus, abnormal gait, (The Oxcarbazepine Pediatric Study Group). 22. 5.
Structurally related to tricyclic antidepressants (TCAs) but lacks antidepressant properties.
A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in children and adolescents with epilepsy. Bill PA, Vigonius U, Pohlmann H et al. 7.
Rockville, MD; 2009 May 5. Rockville, MD; 2008 Jan 31. 150 mg, 300 mg, 600 mg tablets; 300 mg/5 mL suspensionStructurally related to tricyclic antidepressants (TCAs) but lacks antidepressant properties.
Beydoun A.
Pediatric Use.
Novartis, East Hanover, NJ: Personal communication.13.
Practice guideline for the treatment of patients with bipolar disorder (revision). American Psychiatric Association. Scachter SC. Christe W, Kramer G, Vigonius U et al.
Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. FDA Alert: Information for healthcare professionals: suicidality and antiepileptic drugs. Depakote (divalproex) is good for long-term prevention of seizures, manic episodes in bipolar disorder, and migraines. 6.
Suicidal behavior and ideation and antiepileptic drugs: update 5/5/2009. The next wave of anticonvulsants: focus on levetiracetam, oxcarbazepine, and zonisamide.
Guerreiro MM, Vigonius U, Pohlmann H et al. Available for Android and iOS devices. Oxcarbazepine adjunctive therapy in infants and young children with partial seizures. 18.