Oxcarbazepine
FULL PRESCRIBING INFORMATION: CONTENTS*
- OXCARBAZEPINE DESCRIPTION
- CLINICAL PHARMACOLOGY
- PHARMACODYNAMICS
- PHARMACOKINETICS
- CLINICAL STUDIES
- INDICATIONS & USAGE
- OXCARBAZEPINE CONTRAINDICATIONS
- WARNINGS
- PRECAUTIONS
- INFORMATION FOR PATIENTS
- LABORATORY TESTS
- DRUG INTERACTIONS
- DRUG & OR LABORATORY TEST INTERACTIONS
- CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
- PREGNANCY
- LABOR & DELIVERY
- NURSING MOTHERS
- PEDIATRIC USE
- GERIATRIC USE
- OXCARBAZEPINE ADVERSE REACTIONS
- DRUG ABUSE AND DEPENDENCE
- OVERDOSAGE
- DOSAGE & ADMINISTRATION
- HOW SUPPLIED
- STORAGE AND HANDLING
- INACTIVE INGREDIENT
- PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
FULL PRESCRIBING INFORMATION
OXCARBAZEPINE DESCRIPTION
PRECAUTIONS
CLINICAL PHARMACOLOGY
Mechanism of ActionMetabolism and Excretion
PHARMACODYNAMICS
PHARMACOKINETICS
PharmacokineticsEffect of Food
Distribution
Metabolism and Excretion
Special Populations
Hepatic Impairment
Renal Impairment
PRECAUTIONSDOSAGE AND ADMINISTRATION
Pediatric Use
Geriatric Use
Gender
Race
CLINICAL STUDIES
Oxcarbazepine Monotherapy Trials
Figure 1
Figure 2
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Figure 4
Oxcarbazepine Adjunctive Therapy Trials
ADVERSE REACTIONS
TrialTreatment GroupNBaseline MedianMedian %Seizure Rate*Reduction*
Subset analyses of the antiepileptic efficacy of Oxcarbazepine with regard to gender in these trials revealed no important differences in response between men and women. Because there were very few patients over the age of 65 in controlled trials, the effect of the drug in the elderly has not been adequately assessed.
The third adjunctive therapy trial enrolled 128 pediatric patients (1 month to <4 years of age) with inadequately-controlled partial seizures on 1-2 concomitant AEDs. Patients who experienced at least 2 study-specific seizures (i.e., electrographic partial seizures with a behavioral correlate) during the 72-hour baseline period were randomly assigned to either Oxcarbazepine 10 mg/kg/day or were titrated up to 60 mg/kg/day within 26 days. Patients were maintained on their randomized target dose for 9 days and seizures were recorded through continuous video-EEG monitoring during the last 72 hours of the maintenance period. The primary measure of effectiveness in this trial was a between-group comparison of the change in seizure frequency per 24 hours compared to the seizure frequency at baseline. For the entire group of patients enrolled, this comparison was statistically significant in favor of Oxcarbazepine 60 mg/kg/day. In this study, there was no evidence that Oxcarbazepine was effective in patients below the age of 2 years (N=75).
INDICATIONS & USAGE
OXCARBAZEPINE CONTRAINDICATIONS
WARNINGS
WARNINGSHyponatremia
Anaphylactic Reactions and Angioedema
WARNINGS, Patients with a Past History of Hypersensitivity Reaction to Carbamazepine
Patients with a Past History of Hypersensitivity Reaction to Carbamazepine
WARNINGS, Anaphylactic Reactions and AngioedemaPRECAUTIONS, Multi-Organ Hypersensitivitysubsection).
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. The median time of onset for reported cases was 19 days. Such serious skin reactions may be life threatening, and some patients have required hospitalization with very rare reports of fatal outcome. 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.
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), 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 four 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 (5-100 years) in the clinical trials analyzed. Table 2 shows absolute and relative risk by indication for all evaluated AEDs.
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
Indi-Placebo PatientsDrug PatientsRelative Risk: Incidence ofRisk Difference:cati-with Events Perwith Events Perof Events in Drug Patients/Additional Drug Patientson1,000 Patients1,000 PatientsIncidence in Placebo Patientswith Events Per 1,000PatientsEpil-1.03.43.52.4epsyPsy-5.78.51.52.9chiatricOther1.01.81.90.9Total2.44.31.81.9The 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.
Withdrawal of AEDs
As with all antiepileptic drugs, Oxcarbazepine should be withdrawn gradually to minimize the potential of increased seizure frequency.
PRECAUTIONS
PRECAUTIONSFD&C Yellow No. 5 (Tartrazine)
Cognitive/Neuropsychiatric Adverse Events
Adult Patients
Pediatric Patients
Multi-Organ Hypersensitivity
WARNINGS, Patients with a Past History of Hypersensitivity Reaction to Carbamazepine
INFORMATION FOR PATIENTS
Information for PatientsWARNINGS, Anaphylactic Reactions and Angioedema
WARNINGS, Patients with a Past History of Hypersensitivity Reaction to Carbamazepine
WARNINGS, Serious Dermatological Reactions
PRECAUTIONS, Multi-Organ Hypersensitivity
Drug Interactions
PRECAUTIONS, Pregnancy Category C
LABORATORY TESTS
Laboratory TestsWARNINGS
DRUG INTERACTIONS
Drug InteractionsAntiepileptic Drugs
AEDDoseOxcarb-Influence of Oxcarbazepine on AEDInfluence of AED on MHDCoadmi-ofazepineConcentration (Mean Change, 90%Concentration (Mean Change,nisteredAEDDoseConfidence Interval)90% Confidence Interval)(mg/(mg/day)day)****
Hormonal Contraceptives
Drug Interactions
Calcium Antagonists
Other Drug Interactions
DRUG & OR LABORATORY TEST INTERACTIONS
Drug/Laboratory Test InteractionsCARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
Carcinogenesis/Mutagenesis/Impairment of Fertility
PREGNANCY
Pregnancy Category CLABOR & DELIVERY
Labor and DeliveryNURSING MOTHERS
Nursing MothersPatients with Renal Impairment
CLINICAL PHARMACOLOGY, Pharmacokinetics
PEDIATRIC USE
Pediatric UseADVERSE REACTIONS
GERIATRIC USE
Geriatric UseOXCARBAZEPINE ADVERSE REACTIONS
Most Common Adverse Events in All Clinical StudiesAdjunctive Therapy/Monotherapy in Adults Previously Treated with other AEDs
Monotherapy in Adults Not Previously Treated with other AEDs
Adjunctive Therapy/Monotherapy in Pediatric Patients 4 Years Old and Above Previously Treated with other AEDs
Monotherapy in Pediatric Patients 4 Years Old and Above not Previously Treated with other AEDs
Adjunctive Therapy/Monotherapy in Pediatric Patients 1 month to < 4 Years Old Previously Treated or not Previously Treated with other AEDs
Incidence in Controlled Clinical Studies
Controlled Clinical Studies of Adjunctive Therapy/Monotherapy in Adults Previously Treated with other AEDs
Oxcarbazepine Dosage (mg/day)Body System/OXC 600OXC 1200OXC 2400PlaceboAdverse EventN=163N=171N=126N=166%%%%Body as a WholeCardiovascular SystemDigestive SystemMetabolic and Nutritional DisordersMusculoskeletal SystemNervous SystemRespiratory SystemSkin and AppendagesSpecial Senses
Oxcarbazepine Dosage (mg/day)Body System/2400300Adverse EventN=86N=86%%Body as a WholeDigestive SystemHemic and Lymphatic SystemInfections and InfestationsMetabolic and Nutritional DisordersNervous SystemSkin and AppendagesSpecial SensesUrogenital and Reproductive System
Controlled Clinical Study of Monotherapy in Adults not Previously Treated with other AEDs
Body System/OxcarbazepinePlaceboAdverse EventN=55N=49%%Body as a WholeDigestive SystemMusculoskeletal SystemNervous SystemRespiratory SystemSkin and Appendages
Controlled Clinical Studies of Adjunctive Therapy/Monotherapy in Pediatric Patients Previously Treated with other AEDs
Body System/OxcarbazepinePlaceboAdverse EventN=171N=139%%Body as a WholeDigestive SystemNervous SystemRespiratory SystemSkin and AppendagesSpecial Senses
Other Events Observed in Association with the Administration of Oxcarbazepine
Post-Marketing and Other Experience
PRECAUTIONS, Multi-Organ Hypersensitivity
WARNINGS, Anaphylactic Reactions and Angioedema
WARNINGS, Serious Dermatological Reactions
DRUG ABUSE AND DEPENDENCE
AbuseDependence
OVERDOSAGE
OVERDOSAGEHuman Overdose Experience
Treatment and Management
DOSAGE & ADMINISTRATION
CLINICAL PHARMACOLOGY, Pharmacokinetics
Adults
Adjunctive Therapy
PRECAUTIONS, Drug Interactions
Conversion to Monotherapy
Initiation of Monotherapy
Pediatric Patients
Adjunctive Therapy (Aged 2-16 years)
CLINICAL PHARMACOLOGY
Conversion to Monotherapy (Aged 4-16 years)
Initiation of Monotherapy (Aged 4-16 years)
FromToWeight in kgDose (mg/day)Dose (mg/day)
Patients with Hepatic Impairment
CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations
Patients with Renal Impairment
CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations
HOW SUPPLIED
STORAGE AND HANDLING
INACTIVE INGREDIENT
INACTIVE INGREDIENTS:CROSPOVIDONE
SILICON DIOXIDE
HYPROMELLOSES
MAGNESIUM STEARATE
CELLULOSE, MICROCRYSTALLINE
POLYETHYLENE GLYCOL
TITANIUM DIOXIDE
FD&C YELLOW NO. 6
FD&C YELLOW NO. 5
FD&C BLUE NO. 2
POLYVINYL ALCOHOL
ALUMINUM OXIDE
LECITHIN, SOYBEAN
TALC
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
OxcarbazepineOxcarbazepine TABLET
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