Oxcarbazepine

Prescription

Handelsnamen: Oxcarbazepine

Darreichungsform

Tablet

Applikationsweg

ORAL

Hersteller

REMEDYREPACK INC.

About This Medication

11 DESCRIPTION Oxcarbazepine is an AED antiepileptic drug available as 150 mg, 300 mg, and 600 mg film-coated tablets for oral administration. Oxcarbazepine is 10,11-Dihydro-10-oxo-5 H -dibenz[b, f ]azepine-5-carboxamide, and its structural formula is: Oxcarbazepine USP is a light orange to creamish white or off-white powder. Sparingly soluble in acetic acid, slightly soluble in chloroform and practically insoluble in water. Its molecular weight is 252.268. Oxcarbazepine film-coated tablets USP contain the following inactive ingredients: colloidal silicon dioxide, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, black iron oxide, iron oxide yellow, iron oxide red, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. oxcarbazepinetabstruct

Wirkstoffe

Wirkstoff	Stärke
Oxcarbazepine	-

Indikationen und Anwendung

1 INDICATIONS AND USAGE Oxcarbazepine tablets are indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. Oxcarbazepine tablets are indicated for: • Adults: Monotherapy or adjunctive therapy in the treatment of partial-onset seizures • Pediatrics: - Monotherapy in the treatment of partial-onset seizures in children 4 to 16 years - Adjunctive therapy in the treatment of partial-onset seizures in children 2 to 16 years ( 1 )

So funktioniert es

12.1 Mechanism of Action The pharmacological activity of oxcarbazepine is primarily exerted through the 10-monohydroxy metabolite (MHD) of oxcarbazepine [see Clinical Pharmacology ( 12.3 )]. The precise mechanism by which oxcarbazepine and MHD exert their anti-seizure effect is unknown; however, in vitro electrophysiological studies indicate that they produce blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminution of propagation of synaptic impulses. These actions are thought to be important in the prevention of seizure spread in the intact brain. In addition, increased potassium conductance and modulation of high-voltage activated calcium channels may contribute to the anticonvulsant effects of the drug. No significant interactions of oxcarbazepine or MHD with brain neurotransmitter or modulator receptor sites have been demonstrated.

Dosierung und Verabreichung

2 DOSAGE AND ADMINISTRATION Adults : initiate with a dose of 600 mg/day, given twice a day • Adjunctive Therapy: Maximum increment of 600 mg/day at approximately weekly intervals. The recommended daily dose is 1200 mg/day ( 2.1 ) • Conversion to Monotherapy: Withdrawal concomitant over 3 to 6 weeks; reach maximum dose of oxcarbazepine tablets in 2 to 4 weeks with increments of 600 mg/day at weekly intervals to a recommended daily dose of 2400 mg/day ( 2.2 ) • Initiation of Monotherapy: Increments of 300 mg/day every third day to a dose of 1200 mg/day ( 2.3 ) • Initiate at one-half the usual starting dose and increase slowly in patients with a creatinine clearance < 30 mL/min ( 2.7 ) Pediatrics : initiation with 8 to 10 mg/kg/day, given twice a day. For patients aged 2 to < 4 years and under 20 kg, a starting dose of 16 to 20 mg/kg/day may be considered. Recommended daily dose is dependent upon patient weight. • Adjunctive Patients (Aged 2 to 16 Years): For patients aged 4 to 16 years, target maintenance dose should be achieved over 2 weeks ( 2.4 ). For patients aged 2 to < 4 years, maximum maintenance dose should be achieved over 2 to 4 weeks and should not exceed 60 mg/kg/day ( 2.4 ) • Conversion to Monotherapy for Patients (Aged 4 to 16 Years): Maximum increment of 10 mg/kg/day at weekly intervals, concomitant antiepileptic drugs (AEDs) can be completely withdrawn over 3 to 6 weeks ( 2.5 ) • Initiation of Monotherapy for Patients (Aged 4 to 16 Years): Increments of 5 mg/kg/day every third day ( 2.6 ) 2.1 Adjunctive Therapy for Adults Initiate oxcarbazepine tablets with a dose of 600 mg/day, given twice a day. If clinically indicated, the dose may be increased by a maximum of 600 mg/day at approximately weekly intervals; the maximum recommended daily dose is 1200 mg/day. Daily doses above 1200 mg/day show somewhat greater effectiveness in controlled trials, but most patients were not able to tolerate the 2400 mg/day dose, primarily because of central nervous (CNS) effects. Dosage adjustment is recommended with concomitant use of strong CYP3A4 enzyme inducers or UDP-glucuronosyltransferases (UGT) inducers, which include certain antiepileptic drugs (AEDs) [ see Drug Interactions ( 7.1 , 7.2 ) ]. 2.2 Conversion to Monotherapy for Adults Patients receiving concomitant AEDs may be converted to monotherapy by initiating treatment with oxcarbazepine tablets at 600 mg/day (given in a twice a day regimen) while simultaneously initiating the reduction of the dose of the concomitant AEDs. The concomitant AEDs should be completely withdrawn over 3 to 6 weeks, while the maximum dose of oxcarbazepine tablets should be reached in about 2 to 4 weeks. Oxcarbazepine tablets may be increased as clinically indicated by a maximum increment of 600 mg/day at approximately weekly intervals to achieve the maximum recommended daily dose of 2400 mg/day. A daily dose of 1200 mg/day has been shown in one study to be effective in patients in whom monotherapy has been initiated with oxcarbazepine tablets. Patients should be observed closely during this transition phase. 2.3 Initiation of Monotherapy for Adults Patients not currently being treated with AEDs may have monotherapy initiated with oxcarbazepine tablets. In these patients, initiate oxcarbazepine tablets at a dose of 600 mg/day (given a twice a day); the dose should be increased by 300 mg/day every third day to a dose of 1200 mg/day. Controlled trials in these patients examined the effectiveness of a 1200 mg/day dose; a dose of 2400 mg/day has been shown to be effective in patients converted from other AEDs to oxcarbazepine tablets monotherapy (see above). 2.4 Adjunctive Therapy for Pediatric Patients (Aged 2 to 16 Years) In pediatric patients aged 4 to 16 years, initiate oxcarbazepine tablets at a daily dose of 8 to 10 mg/kg generally not to exceed 600 mg/day, given twice a day. The target maintenance dose of oxcarbazepine tablets should be achieved over 2 weeks, and is dependent upon patient weight, according to the following chart: • 20 to 29 kg-900 mg/day • 29.1 to 39 kg-1200 mg/day • 39 kg-1800 mg/day In the clinical trial, in which the intention was to reach these target doses, the median daily dose was 31 mg/kg with a range of 6 to 51 mg/kg. In pediatric patients aged 2 to < 4 years, initiate oxcarbazepine tablets at a daily dose of 8 to 10 mg/kg generally not to exceed 600 mg/day, given twice a day. For patients less than 20 kg, a starting dose of 16 to 20 mg/kg may be considered [ see Clinical Pharmacology ( 12.3 ) ]. The maximum maintenance dose of oxcarbazepine tablets should be achieved over 2 to 4 weeks and should not exceed 60 mg/kg/day in a twice a day regimen. In the clinical trial in pediatric patients (2 to 4 years of age), in which the intention was to reach the target dose of 60 mg/kg/day, 50% of patients reached a final dose of at least 55 mg/kg/day. Under adjunctive therapy (with and without enzyme-inducing AEDs), when normalized by body weight, apparent clearance (L/hr/kg) decreased when age increased such that children 2 to < 4 years of age may require up to twice the oxcarbazepine 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. Dosage adjustment is recommended with concomitant use of strong CYP3A4 enzyme inducers or UGT inducers, which include certain AEDs [see Drug Interactions ( 7.1 , 7.2 )]. 2.5 Conversion to Monotherapy for Pediatric Patients (Aged 4 to 16 Years) Patients receiving concomitant AEDs may be converted to monotherapy by initiating treatment with oxcarbazepine tablets at approximately 8 to 10 mg/kg/day given twice a day, while simultaneously initiating the reduction of the dose of the concomitant AEDs. The concomitant AEDs can be completely withdrawn over 3 to 6 weeks, while oxcarbazepine tablets may be increased as clinically indicated by a maximum increment of 10 mg/kg/day at approximately weekly intervals to achieve the recommended daily dose. Patients should be observed closely during this transition phase. The recommended total daily dose of oxcarbazepine tablets is shown in Table 1. 2.6 Initiation of Monotherapy for Pediatric Patients (Aged 4 to 16 Years) Patients not currently being treated with AEDs may have monotherapy initiated with oxcarbazepine tablets. In these patients, initiate oxcarbazepine tablets at a dose of 8 to 10 mg/kg/day given twice a day. The dose should be increased by 5 mg/kg/day every third day to the recommended daily dose shown in the table below. Table 1: Range of Maintenance Doses of Oxcarbazepine Tablets for Pediatrics by Weight During Monotherapy Weight in kg From To Dose (mg/day) Dose (mg/day) 20 600 900 25 900 1200 30 900 1200 35 900 1500 40 900 1500 45 1200 1500 50 1200 1800 55 1200 1800 60 1200 2100 65 1200 2100 70 1500 2100 2.7 Dosage Modification for Patients With Renal Impairment In patients with impaired renal function (creatinine clearance < 30 mL/min), initiate oxcarbazepine tablets at one-half the usual starting dose (300 mg/day, given twice a day), and increase slowly to achieve the desired clinical response [ see Clinical Pharmacology ( 12.3 ) ]. 2.8 Administration Information Oxcarbazepine tablets can be taken with or without food [ see Clinical Pharmacology ( 12.3 ) ]. Oxcarbazepine oral suspension and oxcarbazepine tablets may be interchanged at equal doses.

Side Effects Overview

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Hyponatremia [see Warnings and Precautions ( 5.1 )] • Anaphylactic Reactions and Angioedema [see Warnings and Precautions ( 5.2 )] • Cross Hypersensitivity Reaction to Carbamazepine [see Warnings and Precautions ( 5.3 )] • Serious Dermatological Reactions [see Warnings and Precautions ( 5.4 )] • Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.5 )] • Cognitive/Neuropsychiatric Adverse Reactions [see Warnings and Precautions ( 5.7 )] • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity [see Warnings and Precautions ( 5.8 )] • Hematologic Events [see Warnings and Precautions ( 5.9 )] The most common (≥ 10% more than placebo for adjunctive or low dose for monotherapy) adverse reactions in adults and pediatrics were: dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, headache, nystagmus, tremor, and abnormal gait ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Annora Pharma Private Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Most Common Adverse Reactions in All Clinical Studies Adjunctive Therapy/Monotherapy in Adults Previously Treated With Other AEDs The most common (≥ 10% more than placebo for adjunctive or low dose for monotherapy) adverse reactions with oxcarbazepine: dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, headache, nystagmus tremor, and abnormal gait. Approximately 23% of these 1537 adult patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: dizziness (6.4%), diplopia (5.9%), ataxia (5.2%), vomiting (5.1%), nausea (4.9%), somnolence (3.8%), headache (2.9%), fatigue (2.1%), abnormal vision (2.1%), tremor (1.8%), abnormal gait (1.7%), rash (1.4%), and hyponatremia (1.0%). Monotherapy in Adults Not Previously Treated With Other AEDs The most common (≥ 5%) adverse reactions with oxcarbazepine in these patients were similar to those in previously treated patients. Approximately 9% of these 295 adult patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: dizziness (1.7%), nausea (1.7%), rash (1.7%), and headache (1.4%). Adjunctive Therapy/Monotherapy in Pediatric Patients 4 Years Old and Above Previously Treated With Other AEDs The most common (≥ 5%) adverse reactions with oxcarbazepine in these patients were similar to those seen in adults. Approximately 11% of these 456 pediatric patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: somnolence (2.4%), vomiting (2.0%), ataxia (1.8%), diplopia (1.3%), dizziness (1.3%), fatigue (1.1%), and nystagmus (1.1%). Monotherapy in Pediatric Patients 4 Years Old and Above Not Previously Treated With Other AEDs The most common (≥ 5%) adverse reactions with oxcarbazepine in these patients were similar to those in adults. Approximately 9.2% of 152 pediatric patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated (≥ 1%) with discontinuation were rash (5.3%) and maculopapular rash (1.3%). Adjunctive Therapy/Monotherapy in Pediatric Patients 1 Month to < 4 Years Old Previously Treated or Not Previously Treated with Other AEDs: The most common (≥ 5%) adverse reactions with oxcarbazepine in these patients were similar to those seen in older children and adults, except for infections and infestations which were more frequently seen in these younger children. Approximately 11% of these 241 pediatric patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: convulsions (3.7%), status epilepticus (1.2%), and ataxia (1.2%). Controlled Clinical Studies of Adjunctive Therapy/Monotherapy in Adults Previously Treated With Other AEDs Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy, treated with oxcarbazepine or placebo as adjunctive treatment and were numerically more common in the patients treated with any dose of oxcarbazepine. Table 4 lists adverse reactions in patients converted from other AEDs to either high-dose oxcarbazepine (2400 mg/day) or low-dose (300 mg/day) oxcarbazepine. Note that in some of these monotherapy studies patients who dropped out during a preliminary tolerability phase are not included in the tables. Table 3: Adverse Reactions in a Controlled Clinical Study of Adjunctive Therapy With Oxcarbazepine in Adults Body system/ Adverse reaction Oxcarbazepine dosage (mg/day) Oxcarbazepine 600 N=163 % Oxcarbazepine 1200 N=171 % Oxcarbazepine 2400 N=126 % Placebo N=166 % Body as a whole Fatigue 15 12 15 7 Asthenia 6 3 6 5 Leg edema 2 1 2 1 Increased weight 1 2 2 1 Feeling abnormal 0 1 2 0 Cardiovascular system Hypotension 0 1 2 0 Digestive system Nausea 15 25 29 10 Vomiting 13 25 36 5 Abdominal pain 10 13 11 5 Diarrhea 5 6 7 6 Dyspepsia 5 5 6 2 Constipation 2 2 6 4 Gastritis 2 1 2 1 Metabolic and nutritional disorders Hyponatremia 3 1 2 1 Musculoskeletal system Muscle weakness 1 2 2 0 Sprains and strains 0 2 2 1 Nervous system Headache 32 28 26 23 Dizziness 26 32 49 13 Somnolence 20 28 36 12 Ataxia 9 17 31 5 Nystagmus 7 20 26 5 Abnormal gait 5 10 17 1 Insomnia 4 2 3 1 Tremor 3 8 16 5 Nervousness 2 4 2 1 Agitation 1 1 2 1 Abnormal coordination 1 3 2 1 Abnormal EEG 0 0 2 0 Speech disorder 1 1 3 0 Confusion 1 1 2 1 Cranial injury NOS 1 0 2 1 Dysmetria 1 2 3 0 Abnormal thinking 0 2 4 0 Respiratory system Rhinitis 2 4 5 4 Skin and appendages Acne 1 2 2 0 Special senses Diplopia 14 30 40 5 Vertigo 6 12 15 2 Abnormal vision 6 14 13 4 Abnormal accommodation 0 0 2 0 Abbreviations: EEG, electroencephalogram; NOS, not otherwise specified. Table 4: Adverse Reactions in Controlled Clinical Studies of Monotherapy With Oxcarbazepine in Adults Previously Treated With Other Antiepileptic Drugs Body system/ Adverse reaction Oxcarbazepine dosage (mg/day) Oxcarbazepine 2400 mg/day N = 86 % Oxcarbazepine 300 mg/day N = 86 % Body as a whole Fatigue 21 5 Fever 3 0 Allergy 2 0 Generalized edema 2 1 Chest pain 2 0 Digestive system Nausea 22 7 Vomiting 15 5 Diarrhea 7 5 Dyspepsia 6 1 Anorexia 5 3 Abdominal pain 5 3 Dry mouth 3 0 Hemorrhage rectum 2 0 Toothache 2 1 Hemic and lymphatic system Lymphadenopathy 2 0 Infections and infestations Viral infection 7 5 Infection 2 0 Metabolic and nutritional disorders Hyponatremia 5 0 Thirst 2 0 Nervous system Headache 31 15 Dizziness 28 8 Somnolence 19 5 Anxiety 7 5 Ataxia 7 1 Confusion 7 0 Nervousness 7 0 Insomnia 6 3 Tremor 6 3 Amnesia 5 1 Aggravated convulsions 5 2 Emotional lability 3 2 Hypoesthesia 3 1 Abnormal coordination 2 1 Nystagmus 2 0 Speech disorder 2 0 Respiratory system Upper respiratory tract infection 10 5 Coughing 5 0 Bronchitis 3 0 Pharyngitis 3 0 Skin and appendages Hot flushes 2 1 Purpura 2 0 Special senses Abnormal vision 14 2 Diplopia 12 1 Taste perversion 5 0 Vertigo 3 0 Earache 2 1 Ear infection NOS 2 0 Urogenital and reproductive system Urinary tract infection 5 1 Micturition frequency 2 1 Vaginitis 2 0 Abbreviation: NOS, not otherwise specified. Controlled Clinical Study of Monotherapy in Adults Not Previously Treated With Other AEDs Table 5 lists adverse reactions in a controlled clinical study of monotherapy in adults not previously treated with other AEDs that occurred in at least 2% of adult patients with epilepsy treated with oxcarbazepine or placebo and were numerically more common in the patients treated with oxcarbazepine. Table 5: Adverse Reactions in a Controlled Clinical Study of Monotherapy With Oxcarbazepine in Adults Not Previously Treated With Other Antiepileptic Drugs Body system/ Adverse reaction Oxcarbazepine N=55 % Placebo N=49 % Body as a whole Falling down NOS 4 0 Digestive system Nausea 16 12 Diarrhea 7 2 Vomiting 7 6 Constipation 5 0 Dyspepsia 5 4 Musculoskeletal system Back pain 4 2 Nervous system Dizziness 22 6 Headache 13 10 Ataxia 5 0 Nervousness 5 2 Amnesia 4 2 Abnormal coordination 4 2 Tremor 4 0 Respiratory system Upper respiratory tract infection 7 0 Epistaxis 4 0 Infection chest 4 0 Sinusitis 4 2 Skin and appendages Rash 4 2 Special senses Vision abnormal 4 0 Abbreviation: NOS, not otherwise specified. Controlled Clinical Studies of Adjunctive Therapy/Monotherapy in Pediatric Patients Previously Treated With Other AEDs Table 6 lists adverse reactions that occurred in at least 2% of pediatric patients with epilepsy treated with oxcarbazepine or placebo as adjunctive treatment and were numerically more common in the patients treated with oxcarbazepine. Table 6: Adverse Reactions in Controlled Clinical Studies of Adjunctive Therapy/Monotherapy With Oxcarbazepine in Pediatric Patients Previously Treated With Other Antiepileptic Drugs Body system/ Adverse reaction Oxcarbazepine N=171 % Placebo N=139 % Body as a whole Fatigue 13 9 Allergy 2 0 Asthenia 2 1 Digestive system Vomiting 33 14 Nausea 19 5 Constipation 4 1 Dyspepsia 2 0 Nervous system Headache 31 19 Somnolence 31 13 Dizziness 28 8 Ataxia 13 4 Nystagmus 9 1 Emotional lability 8 4 Abnormal gait 8 3 Tremor 6 4 Speech disorder 3 1 Impaired concentration 2 1 Convulsions 2 1 Involuntary muscle contractions 2 1 Respiratory system Rhinitis 10 9 Pneumonia 2 1 Skin and appendages Bruising 4 2 Increased sweating 3 0 Special senses Diplopia 17 1 Abnormal vision 13 1 Vertigo 2 0 Other Events Observed in Association With the Administration of Oxcarbazepine In the paragraphs that follow, the adverse reactions, other than those in the preceding tables or text, that occurred in a total of 565 children and 1574 adults exposed to oxcarbazepine and that are reasonably likely to be related to drug use are presented. Events common in the population, events reflecting chronic illness and events likely to reflect concomitant illness are omitted particularly if minor. They are listed in order of decreasing frequency. Because the reports cite events observed in open label and uncontrolled trials, the role of oxcarbazepine in their causation cannot be reliably determined. Body as a Whole: fever, malaise, pain chest precordial, rigors, weight decrease Cardiovascular System: bradycardia, cardiac failure, cerebral hemorrhage, hypertension, hypotension postural, palpitation, syncope, tachycardia Digestive System: appetite increased, blood in stool, cholelithiasis, colitis, duodenal ulcer, dysphagia, enteritis, eructation, esophagitis, flatulence, gastric ulcer, gingival bleeding, gum hyperplasia, hematemesis, hemorrhage rectum, hemorrhoids, hiccup, mouth dry, pain biliary, pain right hypochondrium, retching, sialoadenitis, stomatitis, stomatitis ulcerative Hematologic and Lymphatic System: thrombocytopenia Laboratory Abnormality: gamma-GT increased, hyperglycemia, hypocalcemia, hypoglycemia, hypokalemia, liver enzymes elevated, serum transaminase increased Musculoskeletal System: hypertonia muscle Nervous System: aggressive reaction, amnesia, anguish, anxiety, apathy, aphasia, aura, convulsions aggravated, delirium, delusion, depressed level of consciousness, dysphonia, dystonia, emotional lability, euphoria, extrapyramidal disorder, feeling drunk, hemiplegia, hyperkinesia, hyperreflexia, hypoesthesia, hypokinesia, hyporeflexia, hypotonia, hysteria, libido decreased, libido increased, manic reaction, migraine, muscle contractions involuntary, nervousness, neuralgia, oculogyric crisis, panic disorder, paralysis, paroniria, personality disorder, psychosis, ptosis, stupor, tetany Respiratory System: asthma, dyspnea, epistaxis, laryngismus, pleurisy Skin and Appendages: acne, alopecia, angioedema, bruising, dermatitis contact, eczema, facial rash, flushing, folliculitis, heat rash, hot flushes, photosensitivity reaction, pruritus genital, psoriasis, purpura, rash erythematous, rash maculopapular, vitiligo, urticarial Special Senses: accommodation abnormal, cataract, conjunctival hemorrhage, edema eye, hemianopia, mydriasis, otitis externa, photophobia, scotoma, taste perversion, tinnitus, xerophthalmia Surgical and Medical Procedures: procedure dental oral, procedure female reproductive, procedure musculoskeletal, procedure skin Urogenital and Reproductive System: dysuria, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, micturition frequency, pain renal, pain urinary tract, polyuria, priapism, renal calculus Other: Systemic lupus erythematosus Laboratory Tests Serum sodium levels below 125 mmol/L have been observed in patients treated with oxcarbazepine [see Warnings and Precautions ( 5.1 )]. Experience from clinical trials indicates that serum sodium levels return toward normal when the oxcarbazepine dosage is reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction). Laboratory data from clinical trials suggest that oxcarbazepine use was associated with decreases in T 4, without changes in T 3 or TSH. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of oxcarbazepine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as a Whole: multi-organ hypersensitivity disorders characterized by features such as rash, fever, lymphadenopathy, abnormal liver function tests, eosinophilia and arthralgia [see Warnings and Precautions ( 5.8 )] Cardiovascular System: atrioventricular block Immune System Disorders: anaphylaxis [see Warnings and Precautions ( 5.2 )] Digestive System: pancreatitis and/or lipase and/or amylase increase Hematologic and Lymphatic Systems: aplastic anemia [see Warnings and Precautions ( 5.9 )] Metabolism and Nutrition Disorders: hypothyroidism and syndrome of inappropriate antidiuretic hormone secretion (SIADH) Skin and Subcutaneous Tissue Disorders: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis [see Warnings and Precautions ( 5.4 )] , Acute Generalized Exanthematous Pustulosis (AGEP) Musculoskeletal, Connective Tissue and Bone Disorders: There have been reports of decreased bone mineral density, osteoporosis, and fractures in patients on long-term therapy with oxcarbazepine. Injury, Poisoning, and Procedural Complications: fall Nervous System Disorders: dysarthria

Warnhinweise und Vorsichtsmaßnahmen

5 WARNINGS AND PRECAUTIONS • Hyponatremia: Monitor serum sodium levels ( 5.1 ) • Cross Hypersensitivity Reaction to Carbamazepine: Discontinue immediately if hypersensitivity occurs ( 5.3 ) • Serious Dermatological Reactions: If occurs, consider discontinuation ( 5.4 ) • Suicidal Behavior and Ideation: Monitor for suicidal thoughts/behavior ( 5.5 ) • Withdrawal of AEDs: Withdraw oxcarbazepine gradually ( 5.6 ) • Cognitive/Neuropsychiatric Adverse Reactions: May cause cognitive dysfunction, somnolence, and coordination abnormalities. Use caution when operating machinery ( 5.7 ) • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity: Monitor and discontinue if another cause cannot be established ( 5.8 ) • Hematologic Events: Consider discontinuing ( 5.9 ) • Seizure Control During Pregnancy: Active metabolite may decrease ( 5.10 ) • Risk of Seizure Aggravation: Discontinue if occurs ( 5.11 ) 5.1 Hyponatremia Clinically significant hyponatremia (sodium < 125 mmol/L) can develop during oxcarbazepine use. In the 14 controlled epilepsy studies, 2.5% of oxcarbazepine-treated patients (38/1524) had a sodium of less than 125 mmol/L at some point during treatment, compared to no such patients assigned placebo or active control (carbamazepine and phenobarbital for adjunctive and monotherapy substitution studies, and phenytoin and valproate for the monotherapy initiation studies). Clinically significant hyponatremia generally occurred during the first 3 months of treatment with oxcarbazepine, although there were patients who first developed a serum sodium < 125 mmol/L more than 1 year after initiation of therapy. Most patients who developed hyponatremia were asymptomatic, but patients in the clinical trials were frequently monitored and some had their oxcarbazepine dose reduced, discontinued, or had their fluid intake restricted for hyponatremia. Whether or not these maneuvers prevented the occurrence of more severe events is unknown. Cases of symptomatic hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported during postmarketing use. In clinical trials, patients whose treatment with oxcarbazepine was discontinued due to hyponatremia generally experienced normalization of serum sodium within a few days without additional treatment. Measurement of serum sodium levels should be considered for patients during maintenance treatment with oxcarbazepine, particularly if the patient is receiving other medications known to decrease serum sodium levels (e.g., drugs associated with inappropriate ADH secretion), or if symptoms possibly indicating hyponatremia develop (e.g., nausea, malaise, headache, lethargy, confusion, obtundation, or increase in seizure frequency or severity). 5.2 Anaphylactic Reactions and Angioedema Rare 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 oxcarbazepine. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with oxcarbazepine, the drug should be discontinued and an alternative treatment started. These patients should not be rechallenged with the drug [see Warnings and Precautions ( 5.3 )]. 5.3 Cross Hypersensitivity Reaction to Carbamazepine Approximately 25% to 30% of patients who have had hypersensitivity reactions to carbamazepine will experience hypersensitivity reactions with oxcarbazepine. For this reason, patients should be specifically questioned about any prior experience with carbamazepine, and patients with a history of hypersensitivity reactions to carbamazepine should ordinarily be treated with oxcarbazepine only if the potential benefit justifies the potential risk. If signs or symptoms of hypersensitivity develop, oxcarbazepine should be discontinued immediately [see Warnings and Precautions ( 5.2 , 5.8 )]. 5.4 Serious Dermatological Reactions Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults in association with oxcarbazepine use. Such serious skin reactions may be life threatening, and some patients have required hospitalization with very rare reports of fatal outcome. The median time of onset for reported cases was 19 days after treatment initiation. Recurrence of the serious skin reactions following rechallenge with oxcarbazepine has also been reported. The reporting rate of TEN and SJS associated with oxcarbazepine use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate estimates by a factor of 3- to 10-fold. Estimates of the background incidence rate for these serious skin reactions in the general population range between 0.5 to 6 cases per million-person years. Therefore, if a patient develops a skin reaction while taking oxcarbazepine, consideration should be given to discontinuing oxcarbazepine use and prescribing another antiepileptic medication. Association With HLA-B*1502 Patients carrying the HLA-B*1502 allele may be at increased risk for SJS/TEN with oxcarbazepine treatment. Human Leukocyte Antigen (HLA) allele B*1502 increases the risk for developing SJS/TEN in patients treated with carbamazepine. The chemical structure of oxcarbazepine is similar to that of carbamazepine. Available clinical evidence, and data from nonclinical studies showing a direct interaction between oxcarbazepine and HLA-B*1502 protein, suggest that the HLA-B*1502 allele may also increase the risk for SJS/TEN with oxcarbazepine. The frequency of HLA-B*1502 allele ranges from 2% to 12% in Han Chinese populations, is about 8% in Thai populations, and above 15% in the Philippines, and in some Malaysian populations. Allele frequencies up to about 2% and 6% have been reported in Korea and India, respectively. The frequency of the HLA-B*1502 allele is negligible in people from European descent, several African populations, indigenous peoples of the Americas, Hispanic populations, and in Japanese (< 1%). Testing for the presence of the HLA-B*1502 allele should be considered in patients with ancestry in genetically at-risk populations, prior to initiating treatment with oxcarbazepine. The use of oxcarbazepine should be avoided in patients positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Consideration should also be given to avoid the use of other drugs associated with SJS/TEN in HLA-B*1502 positive patients, when alternative therapies are otherwise equally acceptable. Screening is not generally recommended in patients from populations in which the prevalence of HLAB* 1502 is low, or in current oxcarbazepine users, as the risk of SJS/TEN is largely confined to the first few months of therapy, regardless of HLA-B*1502 status. The use of HLA-B*1502 genotyping has important limitations, and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as AED dose, compliance, concomitant medications, comorbidities, and the level of dermatologic monitoring have not been well characterized. 5.5 Suicidal Behavior and Ideation Antiepileptic drugs, including oxcarbazepine, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were 4 suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs, and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 2 shows absolute and relative risk by indication for all evaluated AEDs. Table 2: Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo patients with events per 1000 patients Drug patients with events per 1000 patients Relative risk: incidence of events in drug patients/incidence in placebo patients Risk difference: additional drug patients with events per 1000 patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing oxcarbazepine or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. 5.6 Withdrawal of Antiepileptic Drugs As with most AEDs, oxcarbazepine should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus [ see Dosage and Administration ( 2.4 ) and Clinical Studies ( 14 ) ]. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered. 5.7 Cognitive/Neuropsychiatric Adverse Reactions Use of oxcarbazepine has been associated with CNS-related adverse reactions. The most significant of these can be classified into three general categories: 1) cognitive symptoms, including psychomotor slowing, difficulty with concentration, and speech or language problems; 2) somnolence or fatigue; and 3) coordination abnormalities, including ataxia and gait disturbances. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on oxcarbazepine to gauge whether it adversely affects their ability to drive or operate machinery. Adult Patients In one large, fixed-dose study, oxcarbazepine was added to existing AED therapy (up to three concomitant AEDs). By protocol, the dosage of the concomitant AEDs could not be reduced as oxcarbazepine was added, reduction in oxcarbazepine dosage was not allowed if intolerance developed, and patients were discontinued if unable to tolerate their highest target maintenance doses. In this trial, 65% of patients were discontinued because they could not tolerate the 2400 mg/day dose of oxcarbazepine on top of existing AEDs. The adverse events seen in this study were primarily CNS related and the risk for discontinuation was dose related. In this trial, 7.1% of oxcarbazepine-treated patients and 4% of placebo-treated patients experienced a cognitive adverse reaction. The risk of discontinuation for these events was about 6.5 times greater on oxcarbazepine than on placebo. In addition, 26% of oxcarbazepine-treated patients and 12% of placebo-treated patients experienced somnolence. The risk of discontinuation for somnolence was about 10 times greater on oxcarbazepine than on placebo. Finally, 28.7% of oxcarbazepine-treated patients and 6.4% of placebo-treated patients experienced ataxia or gait disturbances. The risk for discontinuation for these events was about 7 times greater on oxcarbazepine than on placebo. In a single placebo-controlled monotherapy trial evaluating 2400 mg/day of oxcarbazepine, no patients in either treatment group discontinued double-blind treatment because of cognitive adverse events, somnolence, ataxia, or gait disturbance. In the 2 dose-controlled conversion to monotherapy trials comparing 2400 mg/day and 300 mg/day oxcarbazepine, 1.1% of patients in the 2400 mg/day group discontinued double-blind treatment because of somnolence or cognitive adverse reactions compared to 0% in the 300 mg/day group. In these trials, no patients discontinued because of ataxia or gait disturbances in either treatment group. Pediatric Patients A study was conducted in pediatric patients (3 to 17 years old) with inadequately controlled partial-onset seizures in which oxcarbazepine was added to existing AED therapy (up to 2 concomitant AEDs). By protocol, the dosage of concomitant AEDs could not be reduced as oxcarbazepine was added. Oxcarbazepine was titrated to reach a target dose ranging from 30 mg/kg to 46 mg/kg (based on a patient’s body weight with fixed doses for predefined weight ranges). Cognitive adverse events occurred in 5.8% of oxcarbazepine-treated patients (the single most common event being concentration impairment, 4 of 138 patients) and in 3.1% of patients treated with placebo. In addition, 34.8% of oxcarbazepine-treated patients and 14.0% of placebo-treated patients experienced somnolence (no patient discontinued due to a cognitive adverse reaction or somnolence). Finally, 23.2% of oxcarbazepine-treated patients and 7.0% of placebo-treated patients experienced ataxia or gait disturbances. Two (1.4%) oxcarbazepine-treated patients and 1 (0.8%) placebo-treated patient discontinued due to ataxia or gait disturbances. 5.8 Drug Reaction With Eosinophilia and Systemic Symptoms/Multi-Organ Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has occurred with oxcarbazepine. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Oxcarbazepine should be discontinued if an alternative etiology for the signs or symptoms cannot be established. 5.9 Hematologic Events Rare reports of pancytopenia, agranulocytosis, and leukopenia have been seen in patients treated with oxcarbazepine during postmarketing experience. Discontinuation of the drug should be considered if any evidence of these hematologic events develops. 5.10 Seizure Control 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 patients be monitored carefully during pregnancy. Close monitoring should continue through the postpartum period because MHD levels may return after delivery. 5.11 Risk of Seizure Aggravation Exacerbation of or new onset primary generalized seizures has been reported with oxcarbazepine. The risk of aggravation of primary generalized seizures is seen especially in children but may also occur in adults. In case of seizure aggravation, oxcarbazepine should be discontinued.

Kontraindikationen

4 CONTRAINDICATIONS Oxcarbazepine tablets are contraindicated in patients with a known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate [ see Warnings and Precautions ( 5.2 , 5.3 ) ]. Known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate ( 4 , 5.2 )

Pharmakokinetik

12.3 Pharmacokinetics Following oral administration of oxcarbazepine tablets, oxcarbazepine is completely absorbed and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD). In a mass balance study in people, only 2% of total radioactivity in plasma was due to unchanged oxcarbazepine, with approximately 70% present as MHD, and the remainder attributable to minor metabolites. The half-life of the parent is about 2 hours, while the half-life of MHD is about 9 hours, so that MHD is responsible for most antiepileptic activity. Absorption Based on MHD concentrations, oxcarbazepine tablets and suspension were shown to have similar bioavailability. After single-dose administration of oxcarbazepine tablets to healthy male volunteers under fasted conditions, the median t max was 4.5 (range, 3 to 13) hours. After single-dose administration of oxcarbazepine oral suspension to healthy male volunteers under fasted conditions, the median t max was 6 hours. Steady-state plasma concentrations of MHD are reached within 2 to 3 days in patients when oxcarbazepine is given twice a day. At steady state the pharmacokinetics of MHD are linear and show dose proportionality over the dose range of 300 to 2400 mg/day. Food has no effect on the rate and extent of absorption of oxcarbazepine from oxcarbazepine tablets. Although not directly studied, the oral bioavailability of the oxcarbazepine suspension is unlikely to be affected under fed conditions. Therefore, oxcarbazepine tablets and suspension can be taken with or without food. Distribution The apparent volume of distribution of MHD is 49 L. Approximately 40% of MHD is bound to serum proteins, predominantly to albumin. Binding is independent of the serum concentration within the therapeutically relevant range. Oxcarbazepine and MHD do not bind to alpha-1-acid glycoprotein. Metabolism and Excretion Oxcarbazepine is rapidly reduced by cytosolic enzymes in the liver to its 10-monohydroxy metabolite, MHD, which is primarily responsible for the pharmacological effect of oxcarbazepine. MHD is metabolized further by conjugation with glucuronic acid. Minor amounts (4% of the dose) are oxidized to the pharmacologically inactive 10,11-dihydroxy metabolite (DHD). Oxcarbazepine is cleared from the body mostly in the form of metabolites which are predominantly excreted by the kidneys. More than 95% of the dose appears in the urine, with less than 1% as unchanged oxcarbazepine. Fecal excretion accounts for less than 4% of the administered dose. Approximately 80% of the dose is excreted in the urine either as glucuronides of MHD (49%) or as unchanged MHD (27%); the inactive DHD accounts for approximately 3% and conjugates of MHD and oxcarbazepine account for 13% of the dose. The half-life of the parent is about 2 hours, while the half-life of MHD is about 9 hours. Specific Populations Geriatrics Following administration of single (300 mg) and multiple (600 mg/day) doses of oxcarbazepine to elderly volunteers (60 to 82 years of age), the maximum plasma concentrations and AUC values of MHD were 30% to 60% higher than in younger volunteers (18 to 32 years of age). Comparisons of creatinine clearance in young and elderly volunteers indicate that the difference was due to age-related reductions in creatinine clearance. Pediatrics Weight-adjusted MHD clearance decreases as age and weight increases, approaching that of adults. The mean weight-adjusted clearance in children 2 years to < 4 years of age is approximately 80% higher on average than that of adults. Therefore, MHD exposure in these children is expected to be about one-half that of adults when treated with a similar weight-adjusted dose. The mean weight-adjusted clearance in children 4 to 12 years of age is approximately 40% higher on average than that of adults. Therefore, MHD exposure in these children is expected to be about three-quarters that of adults when treated with a similar weight-adjusted dose. As weight increases, for patients 13 years of age and above, the weight-adjusted MHD clearance is expected to reach that of adults. Pediatric Patients With Obesity A population PK analysis of oxcarbazepine was conducted that included n = 92 obese and non-obese pediatric patients < 18 years of age to evaluate the potential impact of obesity on plasma oxcarbazepine exposures. Obesity was defined as BMI ≥ 95th percentile for age and sex based on CDC 2000 growth chart recommendations. Simulated results from this analysis suggested that the target maintenance doses for oxcarbazepine, applied in pediatric patients ≥ 2 years of age, produced equivalent steady-state exposure of MHD between pediatric patients with and without obesity. This finding is consistent when using total body weight, or when using fat-free mass in patients ≥ 3 years and total body weight in patients < 3 years in the simulations. Dosage adjustment according to obesity status is not necessary. Gender No gender-related pharmacokinetic differences have been observed in children, adults, or the elderly. Race No specific studies have been conducted to assess what effect, if any, race may have on the disposition of oxcarbazepine. Renal Impairment There is a linear correlation between creatinine clearance and the renal clearance of MHD. When oxcarbazepine is administered as a single 300 mg dose in renally-impaired patients (creatinine clearance < 30 mL/min), the elimination half-life of MHD is prolonged to 19 hours, with a 2-fold increase in AUC [see Dosage and Administration ( 2.7 ) and Use in Specific Populations ( 8.6 )]. Hepatic Impairment The pharmacokinetics and metabolism of oxcarbazepine and MHD were evaluated in healthy volunteers and hepatically-impaired subjects after a single 900-mg oral dose. Mild-to-moderate hepatic impairment did not affect the pharmacokinetics of oxcarbazepine and MHD [see Dosage and Administration ( 2.8 )]. Pregnancy Due to physiological changes during pregnancy, MHD plasma levels may gradually decrease throughout pregnancy [see Use in Specific Populations ( 8.1 )] Drug Interactions: • In Vitro Oxcarbazepine can inhibit CYP2C19 and induce CYP3A4/5 with potentially important effects on plasma concentrations of other drugs. In addition, several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. No autoinduction has been observed with oxcarbazepine. Oxcarbazepine was evaluated in human liver microsomes to determine its capacity to inhibit the major cytochrome P450 enzymes responsible for the metabolism of other drugs. Results demonstrate that oxcarbazepine and its pharmacologically active 10-monohydroxy metabolite (MHD) have little or no capacity to function as inhibitors for most of the human cytochrome P450 enzymes evaluated (CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP4A9, and CYP4A11) with the exception of CYP2C19 and CYP3A4/5. Although inhibition of CYP3A4/5 by oxcarbazepine and MHD did occur at high concentrations, it is not likely to be of clinical significance. The inhibition of CYP2C19 by oxcarbazepine and MHD can cause increased plasma concentrations of drugs that are substrates of CYP2C19, which is clinically relevant. In vitro , the UDP-glucuronyl transferase level was increased, indicating induction of this enzyme. Increases of 22% with MHD and 47% with oxcarbazepine were observed. As MHD, the predominant plasma substrate, is only a weak inducer of UDP-glucuronyl transferase, it is unlikely to have an effect on drugs that are mainly eliminated by conjugation through UDP-glucuronyl transferase (e.g., valproic acid, lamotrigine). In addition, oxcarbazepine and MHD induce a subgroup of the cytochrome P450 3A family (CYP3A4 and CYP3A5) responsible for the metabolism of dihydropyridine calcium antagonists, oral contraceptives and cyclosporine resulting in a lower plasma concentration of these drugs. As binding of MHD to plasma proteins is low (40%), clinically significant interactions with other drugs through competition for protein binding sites are unlikely. • In Vivo Other Antiepileptic Drugs Potential interactions between oxcarbazepine and other AEDs were assessed in clinical studies. The effect of these interactions on mean AUCs and C min are summarized in Table 7 [see Drug Interactions ( 7.1 , 7.2 )]. Table 7: Summary of Antiepileptic Drug Interactions With Oxcarbazepine AED coadministered Dose of AED (mg/day) Oxcarbazepine dose (mg/day) Influence of Oxcarbazepine on AED concentration (mean change, 90% confidence interval) Influence of AED on MHD concentration (mean change, 90% confidence interval) Carbamazepine 400 to 2000 900 nc 1 40% decrease [CI: 17% decrease, 57% decrease] Phenobarbital 100 to 150 600 to 1800 14% increase [CI: 2% increase, 24% increase] 25% decrease [CI: 12% decrease, 51% decrease] Phenytoin 250 to 500 600 to 1800 > 1200 to 2400 nc 1,2 up to 40% increase 3 [CI: 12% increase, 60% increase] 30% decrease [CI: 3% decrease, 48% decrease] Valproic acid 400 to 2800 600 to 1800 nc 1 18% decrease [CI: 13% decrease, 40% decrease] Lamotrigine 200 1200 nc 1 nc 1 Abbreviations: AED, antiepileptic drugs; CI, confidence interval; MHD, 10-monohydroxy derivative. 1 nc denotes a mean change of less than 10%. 2 Pediatrics. 3 Mean increase in adults at high oxcarbazepine doses. Hormonal Contraceptives Coadministration of oxcarbazepine with an oral contraceptive has been shown to influence the plasma concentrations of the two hormonal components; ethinylestradiol (EE) and levonorgestrel (LNG) [see Drug Interactions ( 7.3 )]. The mean AUC values of EE were decreased by 48% [90% CI: 22 to 65] in one study and 52% [90% CI: 38 to 52] in another study. The mean AUC values of LNG were decreased by 32% [90% CI: 20 to 45] in one study and 52% [90% CI: 42 to 52] in another study. Other Drug Interactions Calcium Antagonists: After repeated coadministration of oxcarbazepine, the AUC of felodipine was lowered by 28% [90% CI: 20 to 33]. Verapamil produced a decrease of 20% [90% CI: 18 to 27] of the plasma levels of MHD. Cimetidine, erythromycin and dextropropoxyphene had no effect on the pharmacokinetics of MHD. Results with warfarin show no evidence of interaction with either single or repeated doses of oxcarbazepine.

Frequently Asked Questions

1 INDICATIONS AND USAGE Oxcarbazepine tablets are indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. Oxcarbazepine tablets are indicated for: • Adults: Monotherapy or adjunctive therapy in the treatment of partial-onset seizures • Pediatrics: - Monotherapy in the treatment of …

2 DOSAGE AND ADMINISTRATION Adults : initiate with a dose of 600 mg/day, given twice a day • Adjunctive Therapy: Maximum increment of 600 mg/day at approximately weekly intervals. The recommended daily dose is 1200 mg/day ( 2.1 ) • Conversion to Monotherapy: Withdrawal concomitant over 3 to 6 weeks; reach maximum dose of oxcarbazepine tablets in 2 to 4 weeks with increments of 600 mg/day at weekly intervals to a recommended daily dose of 2400 mg/day ( 2.2 ) …

5 WARNINGS AND PRECAUTIONS • Hyponatremia: Monitor serum sodium levels ( 5.1 ) • Cross Hypersensitivity Reaction to Carbamazepine: Discontinue immediately if hypersensitivity occurs ( 5.3 ) • Serious Dermatological Reactions: If occurs, consider discontinuation ( 5.4 ) • Suicidal Behavior and Ideation: Monitor for suicidal thoughts/behavior ( 5.5 ) • Withdrawal of AEDs: Withdraw oxcarbazepine gradually ( 5.6 ) • Cognitive/Neuropsychiatric Adverse Reactions: May cause cognitive dysfunction, somnolence, and coordination abnormalities. Use caution when operating machinery ( 5.7 ) …

4 CONTRAINDICATIONS Oxcarbazepine tablets are contraindicated in patients with a known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate [ see Warnings and Precautions ( 5.2 , 5.3 ) ]. Known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate ( 4 , 5.2 )

Oxcarbazepine is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

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References & Data Sources

• DailyMed — Oxcarbazepine drug label (National Library of Medicine)
• openFDA — Oxcarbazepine label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 312137 (NLM Normalized Drug Names)
• NDC Directory — Oxcarbazepine (FDA National Drug Code)

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