OXCARBAZEPINE
Generic: OXCARBAZEPINE
Basic Information
Manufacturer
Apotex Corp.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
a20e4a95-8ee1-e702-003e-e353ec1ee133
Indications & Usage
1 INDICATIONS AND USAGE Oxcarbazepine extended-release tablets are indicated for the treatment of partial-onset seizures in patients 6 years of age and older.
Oxcarbazepine extended-release tablets are indicated for the treatment of partial-onset seizures in patients 6 years of age and older.
( 1 )
Oxcarbazepine extended-release tablets are indicated for the treatment of partial-onset seizures in patients 6 years of age and older.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described in other sections of 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 )] Withdrawal of AEDs [see Warnings and Precautions ( 5.6 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity [see Warnings and Precautions ( 5.7 )] Hematologic Reactions [see Warnings and Precautions ( 5.8 )] Risk of Seizures in the Pregnant Patient [see Warnings and Precautions ( 5.9 )] Most commonly observed (≥5% and more frequent than placebo) adverse reactions in adults were dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, asthenia, and fatigue.
( 6.1 ) Adverse reactions in pediatric patients are similar to those seen in adult patients.
To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp.
at 1-800-706-5575 or contact 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 clinical practice.
The safety data presented below are from 384 patients with partial-onset seizures who received oxcarbazepine extended-release tablets (366 adults and 18 pediatric patients) with concomitant AEDs.
In addition, safety data presented below are from a total of 2,288 patients with seizure disorders treated with immediate-release oxcarbazepine; 1,832 were adults and 456 were pediatric patients.
Most Common Adverse Reactions Reported by Adult Patients Receiving Concomitant AEDs in Oxcarbazepine Extended-Release Tablets Clinical Studies Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with oxcarbazepine extended-release tablets or placebo and concomitant AEDs and that were numerically more common in the patients treated with any dosage of oxcarbazepine extended-release tablets than in patients receiving placebo.
Table 3: Adverse Reaction Incidence in a Controlled Clinical Study of Oxcarbazepine Extended-Release Tablets with Concomitant AEDs in Adults* Oxcarbazepine extended-release tablets 2,400 mg/day N=123 % Oxcarbazepine extended-release tablets 1,200 mg/day N=122 % Placebo N=121 % Any System / Any Term 69 57 55 Nervous System Disorders Dizziness 41 20 15 Somnolence 14 12 9 Headache 15 8 7 Balance Disorder 7 5 5 Tremor 1 5 2 Nystagmus 3 3 1 Ataxia 1 3 1 Gastrointestinal Disorders Vomiting 15 6 9 Abdominal Pain Upper 0 3 1 Dyspepsia 0 3 1 Gastritis 0 3 2 Eye Disorders Diplopia 13 10 4 Vision Blurred 1 4 3 Visual Impairment 1 3 0 General Disorders and Administration Site Conditions Asthenia 7 3 1 Fatigue 3 6 1 Gait Disturbance 0 3 1 Drug Intolerance 2 0 0 Infections and Infestations Nasopharyngitis 0 3 0 Sinusitis 0 3 2 * Reported by ≥ 2% of patients treated with oxcarbazepine extended-release tablets and numerically more frequent than in the placebo group The overall incidence of adverse reactions appeared to be dose related, particularly during the titration period.
The most commonly observed (≥5%) adverse reactions seen in association with oxcarbazepine extended-release tablets and more frequent than in placebo-treated patients were: dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, and asthenia.
Adverse Reactions Associated with Discontinuation of Oxcarbazepine Extended-Release Tablets Treatment: Approximately 23.3% of the 366 adult patients receiving oxcarbazepine extended-release tablets in clinical studies discontinued treatment because of an adverse reaction.
The adverse reactions most commonly associated with discontinuation of oxcarbazepine extended-release tablets (reported by ≥2%) were: dizziness (9.8%), vomiting (5.3%), nausea (3.7%), diplopia (3.2%), and somnolence (2.4%).
Adjunctive Therapy with Oxcarbazepine Extended-Release Tablets in Pediatric Patients 6 to Less than 17 Years of Age Previously Treated with other AEDs In a pharmacokinetic study in 18 pediatric patients (including patients 6 to less than 17 years of age) with partial-onset seizures treated with different dosages of oxcarbazepine extended-release tablets, the observed adverse reactions seen in association with oxcarbazepine extended-release tablets were similar to those seen in adults.
Most Common Adverse Reactions in Immediate-Release Oxcarbazepine Controlled Clinical Studies Controlled Clinical Studies of Adjunctive Therapy with Immediate-Release Oxcarbazepine in Adults Previously Treated with other AEDs: Table 4 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with immediate-release oxcarbazepine or placebo with concomitant AEDs and that were numerically more common in the patients treated with any dosage of immediate-release oxcarbazepine than in placebo.
As immediate-release oxcarbazepine and oxcarbazepine extended-release tablets were not examined in the same trial, adverse event frequencies cannot be directly compared between the two formulations.
Table 4: Adverse Reaction Incidence in a Controlled Clinical Study of Immediate Release Oxcarbazepine with Concomitant AEDs in Adults* Immediate-Release Oxcarbazepine Dosage (mg/day) Placebo N = 166 % OXC 600 N = 163 % OXC 1,200 N = 171 % OXC 2,400 N = 126 % Body as a Whole Fatigue 15 12 15 7 Asthenia 6 3 6 5 Edema Legs 2 1 2 1 Weight Increase 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 Pain Abdominal 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 36 32 49 13 Somnolence 20 28 36 12 Ataxia 9 17 31 5 Nystagmus 7 20 26 5 Gait Abnormal 5 10 17 1 Insomnia 4 2 3 1 Tremor 3 8 16 5 Nervousness 2 4 2 1 Agitation 1 1 2 1 Coordination Abnormal 1 3 2 1 EEG Abnormal 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 Thinking Abnormal 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 Vision Abnormal 6 14 13 4 Accommodation Abnormal 0 0 2 0 * Events in at least 2% of patients treated with 2,400 mg/day of immediate-release oxcarbazepine and numerically more frequent than in the placebo group Other Reactions Observed in Association with the Administration of Immediate-Release 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 1,574 adults exposed to immediate-release 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 reactions observed in open-label and uncontrolled trials, the role of immediate-release 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, bronchitis, coughing, 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, urticaria.
Special Senses: accommodation abnormal, cataract, conjunctival hemorrhage, edema eye, hemianopia, mydriasis, otitis externa, photophobia, scotoma, taste perversion, tinnitus, xerophthalmia.
Urogenital and Reproductive System: dysuria, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, micturition frequency, pain renal, pain urinary tract, polyuria, priapism, renal calculus, urinary tract infection.
Other: Systemic lupus erythematosus.
Laboratory Tests Serum sodium levels below 125 mmol/L have been observed in patients treated with immediate-release oxcarbazepine [see Warnings and Precautions ( 5.1 )] .
Experience from clinical trials with immediate-release oxcarbazepine indicates that serum sodium levels return toward normal when the dosage is reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction).
Laboratory data from clinical trials suggest that immediate-release oxcarbazepine use was associated with decreases in T4, without changes in T3 or TSH.
6.2 Postmarketing and Other Experience The following adverse reactions have been observed in named patient programs or post-marketing experience with immediate-release oxcarbazepine or oxcarbazepine extended-release tablets.
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 ( 5.7 )] Cardiovascular System: atrioventricular block Digestive System: pancreatitis and/or lipase and/or amylase increase Hematologic and Lymphatic Systems: aplastic anemia [see Warnings and Precautions ( 5.8 )] Immune System Disorders: anaphylaxis [see Warnings and Precautions ( 5.2 )] 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 immediate-release oxcarbazepine.
( 6.1 ) Adverse reactions in pediatric patients are similar to those seen in adult patients.
To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp.
at 1-800-706-5575 or contact 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 clinical practice.
The safety data presented below are from 384 patients with partial-onset seizures who received oxcarbazepine extended-release tablets (366 adults and 18 pediatric patients) with concomitant AEDs.
In addition, safety data presented below are from a total of 2,288 patients with seizure disorders treated with immediate-release oxcarbazepine; 1,832 were adults and 456 were pediatric patients.
Most Common Adverse Reactions Reported by Adult Patients Receiving Concomitant AEDs in Oxcarbazepine Extended-Release Tablets Clinical Studies Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with oxcarbazepine extended-release tablets or placebo and concomitant AEDs and that were numerically more common in the patients treated with any dosage of oxcarbazepine extended-release tablets than in patients receiving placebo.
Table 3: Adverse Reaction Incidence in a Controlled Clinical Study of Oxcarbazepine Extended-Release Tablets with Concomitant AEDs in Adults* Oxcarbazepine extended-release tablets 2,400 mg/day N=123 % Oxcarbazepine extended-release tablets 1,200 mg/day N=122 % Placebo N=121 % Any System / Any Term 69 57 55 Nervous System Disorders Dizziness 41 20 15 Somnolence 14 12 9 Headache 15 8 7 Balance Disorder 7 5 5 Tremor 1 5 2 Nystagmus 3 3 1 Ataxia 1 3 1 Gastrointestinal Disorders Vomiting 15 6 9 Abdominal Pain Upper 0 3 1 Dyspepsia 0 3 1 Gastritis 0 3 2 Eye Disorders Diplopia 13 10 4 Vision Blurred 1 4 3 Visual Impairment 1 3 0 General Disorders and Administration Site Conditions Asthenia 7 3 1 Fatigue 3 6 1 Gait Disturbance 0 3 1 Drug Intolerance 2 0 0 Infections and Infestations Nasopharyngitis 0 3 0 Sinusitis 0 3 2 * Reported by ≥ 2% of patients treated with oxcarbazepine extended-release tablets and numerically more frequent than in the placebo group The overall incidence of adverse reactions appeared to be dose related, particularly during the titration period.
The most commonly observed (≥5%) adverse reactions seen in association with oxcarbazepine extended-release tablets and more frequent than in placebo-treated patients were: dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, and asthenia.
Adverse Reactions Associated with Discontinuation of Oxcarbazepine Extended-Release Tablets Treatment: Approximately 23.3% of the 366 adult patients receiving oxcarbazepine extended-release tablets in clinical studies discontinued treatment because of an adverse reaction.
The adverse reactions most commonly associated with discontinuation of oxcarbazepine extended-release tablets (reported by ≥2%) were: dizziness (9.8%), vomiting (5.3%), nausea (3.7%), diplopia (3.2%), and somnolence (2.4%).
Adjunctive Therapy with Oxcarbazepine Extended-Release Tablets in Pediatric Patients 6 to Less than 17 Years of Age Previously Treated with other AEDs In a pharmacokinetic study in 18 pediatric patients (including patients 6 to less than 17 years of age) with partial-onset seizures treated with different dosages of oxcarbazepine extended-release tablets, the observed adverse reactions seen in association with oxcarbazepine extended-release tablets were similar to those seen in adults.
Most Common Adverse Reactions in Immediate-Release Oxcarbazepine Controlled Clinical Studies Controlled Clinical Studies of Adjunctive Therapy with Immediate-Release Oxcarbazepine in Adults Previously Treated with other AEDs: Table 4 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with immediate-release oxcarbazepine or placebo with concomitant AEDs and that were numerically more common in the patients treated with any dosage of immediate-release oxcarbazepine than in placebo.
As immediate-release oxcarbazepine and oxcarbazepine extended-release tablets were not examined in the same trial, adverse event frequencies cannot be directly compared between the two formulations.
Table 4: Adverse Reaction Incidence in a Controlled Clinical Study of Immediate Release Oxcarbazepine with Concomitant AEDs in Adults* Immediate-Release Oxcarbazepine Dosage (mg/day) Placebo N = 166 % OXC 600 N = 163 % OXC 1,200 N = 171 % OXC 2,400 N = 126 % Body as a Whole Fatigue 15 12 15 7 Asthenia 6 3 6 5 Edema Legs 2 1 2 1 Weight Increase 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 Pain Abdominal 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 36 32 49 13 Somnolence 20 28 36 12 Ataxia 9 17 31 5 Nystagmus 7 20 26 5 Gait Abnormal 5 10 17 1 Insomnia 4 2 3 1 Tremor 3 8 16 5 Nervousness 2 4 2 1 Agitation 1 1 2 1 Coordination Abnormal 1 3 2 1 EEG Abnormal 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 Thinking Abnormal 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 Vision Abnormal 6 14 13 4 Accommodation Abnormal 0 0 2 0 * Events in at least 2% of patients treated with 2,400 mg/day of immediate-release oxcarbazepine and numerically more frequent than in the placebo group Other Reactions Observed in Association with the Administration of Immediate-Release 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 1,574 adults exposed to immediate-release 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 reactions observed in open-label and uncontrolled trials, the role of immediate-release 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, bronchitis, coughing, 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, urticaria.
Special Senses: accommodation abnormal, cataract, conjunctival hemorrhage, edema eye, hemianopia, mydriasis, otitis externa, photophobia, scotoma, taste perversion, tinnitus, xerophthalmia.
Urogenital and Reproductive System: dysuria, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, micturition frequency, pain renal, pain urinary tract, polyuria, priapism, renal calculus, urinary tract infection.
Other: Systemic lupus erythematosus.
Laboratory Tests Serum sodium levels below 125 mmol/L have been observed in patients treated with immediate-release oxcarbazepine [see Warnings and Precautions ( 5.1 )] .
Experience from clinical trials with immediate-release oxcarbazepine indicates that serum sodium levels return toward normal when the dosage is reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction).
Laboratory data from clinical trials suggest that immediate-release oxcarbazepine use was associated with decreases in T4, without changes in T3 or TSH.
6.2 Postmarketing and Other Experience The following adverse reactions have been observed in named patient programs or post-marketing experience with immediate-release oxcarbazepine or oxcarbazepine extended-release tablets.
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 ( 5.7 )] Cardiovascular System: atrioventricular block Digestive System: pancreatitis and/or lipase and/or amylase increase Hematologic and Lymphatic Systems: aplastic anemia [see Warnings and Precautions ( 5.8 )] Immune System Disorders: anaphylaxis [see Warnings and Precautions ( 5.2 )] 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 immediate-release oxcarbazepine.