Trileptal is indicated for use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and as monotherapy in the treatment of partial seizures in children aged 4 years and above with epilepsy, and as adjunctive therapy in children aged 2 years and above with partial seizures.
Trileptal Dosage and Administration
All dosing should be given in a twice-a-day regimen. Trileptal oral suspension and Trileptal film-coated tablets may be interchanged at equal doses.
Trileptal should be kept out of the reach and sight of children.
Before using Trileptal oral suspension, shake the bottle well and prepare the dose immediately afterwards. The prescribed amount of oral suspension should be withdrawn from the bottle using the oral dosing syringe supplied. Trileptal oral suspension can be mixed in a small glass of water just prior to administration or, alternatively, may be swallowed directly from the syringe. After each use, close the bottle and rinse the syringe with warm water and allow it to dry thoroughly.
Trileptal can be taken with or without food [see Clinical Pharmacology (12.3)].
Adjunctive Therapy for Adults
Treatment with Trileptal should be initiated with a dose of 600 mg/day, given in a twice-a-day regimen. If clinically indicated, the dose may be increased by a maximum of 600 mg/day at approximately weekly intervals; the 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 CNS effects. It is recommended that the patient be observed closely and plasma levels of the concomitant AEDs be monitored during the period of Trileptal titration, as these plasma levels may be altered, especially at Trileptal doses greater than 1200 mg/day [see Drug Interactions (7.1)].
Conversion to Monotherapy for Adults
Patients receiving concomitant AEDs may be converted to monotherapy by initiating treatment with Trileptal 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 The concomitant AEDs should be completely withdrawn over 3-6 weeks, while the maximum dose of Trileptal should be reached in about 2-4 weeks. Trileptal may be increased as clinically indicated by a maximum increment of 600 mg/day at approximately weekly intervals to achieve the 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 Trileptal. Patients should be observed closely during this transition phase.
Initiation of Monotherapy for Adults
Patients not currently being treated with AEDs may have monotherapy initiated with Trileptal. In these patients, Trileptal should be initiated at a dose of 600 mg/day (given in a twice-a-day regimen); 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 Trileptal monotherapy (see above).
Adjunctive Therapy for Pediatric Patients (Aged 2-16 Years)
In pediatric patients aged 4-16 years, treatment should be initiated at a daily dose of 8-10 mg/kg generally not to exceed 600 mg/day, given in a twice-a-day regimen. The target maintenance dose of Trileptal should be achieved over two weeks, and is dependent upon patient weight, according to the following chart:
20-29 kg - 900 mg/day
29.1-39 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 6-51 mg/kg.
In pediatric patients aged 2-<4 years, treatment should also be initiated at a daily dose of 8-10 mg/kg generally not to exceed 600 mg/day, given in a twice-a-day regimen. For patients under 20 kg, a starting dose of 16-20 mg/kg may be considered [see Clinical Pharmacology (12.3)]. The maximum maintenance dose of Trileptal should be achieved over 2-4 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.
Conversion to Monotherapy for Pediatric Patients (Aged 4-16 Years)
Patients receiving concomitant antiepileptic drugs may be converted to monotherapy by initiating treatment with Trileptal at approximately 8-10 mg/kg/day given in a twice-a-day regimen, while simultaneously initiating the reduction of the dose of the concomitant antiepileptic drugs. The concomitant antiepileptic drugs can be completely withdrawn over 3-6 weeks while Trileptal 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 Trileptal is shown in the table below.
Initiation of Monotherapy for Pediatric Patients (Aged 4-16 Years)
Patients not currently being treated with antiepileptic drugs may have monotherapy initiated with Trileptal. In these patients, Trileptal should be initiated at a dose of 8-10 mg/kg/day given in a twice-a-day regimen. 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 Trileptal for Children by Weight During Monotherapy
|
From |
To |
| Weight in kg |
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 |
Patients with Hepatic Impairment
In general, dose adjustments are not required in patients with mild-to-moderate hepatic impairment [see Clinical Pharmacology (12.3).]
Patients with Renal Impairment
In patients with impaired renal function (creatinine clearance <30 mL/min) Trileptal therapy should be initiated at one-half the usual starting dose (300 mg/day) and increased slowly to achieve the desired clinical response [see Clinical Pharmacology (12.3)]
Dosage Forms and Strengths
Film-coated Tablets: 150 mg, 300 mg and 600 mg. Oral Suspension: 300 mg/5 mL (60 mg/mL)
Contraindications
Trileptal should not be used in patients with a known hypersensitivity to oxcarbazepine or to any of its components.
Warnings and Precautions
Hyponatremia
Clinically significant hyponatremia (sodium <125 mmol/L) can develop during Trileptal use. In the 14 controlled epilepsy studies 2.5% of Trileptal-treated patients (38/1,524) 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 three months of treatment with Trileptal, although there were patients who first developed a serum sodium <125 mmol/L more than one 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 Trileptal 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 have been reported during post-marketing use. In clinical trials, patients whose treatment with Trileptal 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 Trileptal, particularly if the patient is receiving other medications known to decrease serum sodium levels (for example, 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).
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 Trileptal. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with Trileptal, 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)].
Patients with a Past History of Hypersensitivity Reaction to Carbamazepine
Patients who have had hypersensitivity reactions to carbamazepine should be informed that approximately 25%-30% of them will experience hypersensitivity reactions with Trileptal. 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 Trileptal only if the potential benefit justifies the potential risk. If signs or symptoms of hypersensitivity develop, Trileptal should be discontinued immediately [see Warnings and Precautions (5.2, 5.8)].
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 Trileptal 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 Trileptal has also been reported.
The reporting rate of TEN and SJS associated with Trileptal 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 Trileptal, consideration should be given to discontinuing Trileptal use and prescribing another antiepileptic medication.
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including Trileptal, 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 Risk by Indication for Antiepileptic Drugs in the Pooled Analysis
| Indication |
Placebo Patients with Events Per 1,000 Patients
|
Drug Patients with Events Per 1,000 Patients |
Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients |
Risk Difference: Additional Drug Patients with Events Per 1,000 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 Trileptal 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, Trileptal should be withdrawn gradually to minimize the potential of increased seizure frequency.
Cognitive/Neuropsychiatric Adverse Events
Use of Trileptal has been associated with central nervous system-related adverse events. 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.
Adult Patients
In one large, fixed-dose study, Trileptal was added to existing AED therapy (up to three concomitant AEDs). By protocol, the dosage of the concomitant AEDs could not be reduced as Trileptal was added, reduction in Trileptal 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 Trileptal 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 event. 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 seven times greater on oxcarbazepine than on placebo.
In a single placebo-controlled monotherapy trial evaluating 2400 mg/day of Trileptal, no patients in either treatment group discontinued double-blind treatment because of cognitive adverse events, somnolence, ataxia, or gait disturbance.
In the two dose-controlled conversion to monotherapy trials comparing 2400 mg/day and 300 mg/day Trileptal, 1.1% of patients in the 2400 mg/day group discontinued double-blind treatment because of somnolence or cognitive adverse events 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 seizures in which Trileptal was added to existing AED therapy (up to two concomitant AEDs). By protocol, the dosage of concomitant AEDs could not be reduced as Trileptal was added. Trileptal 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 event 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.
Multi-Organ Hypersensitivity
Multi-organ hypersensitivity reactions have occurred in close temporal association (median time to detection 13 days: range 4-60) to the initiation of Trileptal therapy in adult and pediatric patients. Although there have been a limited number of reports, many of these cases resulted in hospitalization and some were considered life threatening. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. These may include hematologic and lymphatic (e.g., eosinophilia, thrombocytopenia, lymphadenopathy, leukopenia, neutropenia, splenomegaly), hepatobiliary (e.g., hepatitis, liver function test abnormalities), renal (e.g., proteinuria, nephritis, oliguria, renal failure), muscles and joints (e.g., joint swelling, myalgia, arthralgia, asthenia), nervous system (e.g., hepatic encephalopathy), respiratory (e.g., dyspnea, pulmonary edema, asthma, bronchospasm, interstitial lung disease), hepatorenal syndrome, pruritus, and angioedema. Because the disorder is variable in its expression, other organ system symptoms and signs, not noted here, may occur. If this reaction is suspected, Trileptal should be discontinued and an alternative treatment started. Although there are no case reports to indicate cross sensitivity with other drugs that produce this syndrome, the experience amongst drugs associated with multi-organ hypersensitivity would indicate this to be a possibility [see Warnings and Precautions (5.3)].
Hematologic Events
Rare reports of pancytopenia, agranulocytosis, and leukopenia have been seen in patients treated with Trileptal during post-marketing experience. Discontinuation of the drug should be considered if any evidence of these hematologic events develop.
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.
Laboratory Tests
Serum sodium levels below 125 mmol/L have been observed in patients treated with Trileptal [see Warnings and Precautions (5.1)]. Experience from clinical trials indicates that serum sodium levels return toward normal when the Trileptal dosage is reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction).
Laboratory data from clinical trials suggest that Trileptal use was associated with decreases in T4, without changes in T3 or TSH.
Adverse Reactions
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.
Clinical Studies Experience
Most Common Adverse Reactions in All Clinical Studies
Adjunctive Therapy/Monotherapy in Adults Previously Treated with other AEDs: The most commonly observed (≥5%) adverse reactions seen in association with Trileptal and substantially more frequent than in placebo-treated patients were: dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, tremor, dyspepsia, abnormal gait.
Approximately 23% of these 1,537 adult patients discontinued treatment because of an adverse experience. 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%), hyponatremia (1.0%).
Monotherapy in Adults Not Previously Treated with other AEDs: The most commonly observed (≥5%) adverse reactions seen in association with Trileptal in these patients were similar to those in previously treated patients.
Approximately 9% of these 295 adult patients discontinued treatment because of an adverse experience. The adverse reactions most commonly associated with discontinuation were: dizziness (1.7%), nausea (1.7%), rash (1.7%), headache (1.4%).
Adjunctive Therapy/Monotherapy in Pediatric Patients 4 Years Old and Above Previously Treated with other AEDs: The most commonly observed (≥5%) adverse reactions seen in association with Trileptal in these patients were similar to those seen in adults.
Approximately 11% of these 456 pediatric patients discontinued treatment because of an adverse experience. 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%), nystagmus (1.1%).
Monotherapy in Pediatric Patients 4 Years Old and Above Not Previously Treated with other AEDs: The most commonly observed (≥5%) adverse reactions seen in association with Trileptal in these patients were similar to those in adults.
Approximately 9.2% of 152 pediatric patients discontinued treatment because of an adverse experience. 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 commonly observed (≥5%) adverse reactions seen in association with Trileptal 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 experience. The adverse reaction most commonly associated with discontinuation were: convulsions (3.7%), status epilepticus (1.2%), and ataxia (1.2%).
Incidence in Controlled Clinical Studies: The prescriber should be aware that the figures in Tables 3, 4, 5 and 6 cannot be used to predict the frequency of adverse reactions in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescriber with one basis to estimate the relative contribution of drug and nondrug factors to the adverse event incidences in the population studied.
Controlled Clinical Studies of Adjunctive Therapy/Monotherapy in Adults Previously Treated with other AEDs: Table 3 lists treatment-emergent signs and symptoms that occurred in at least 2% of adult patients with epilepsy treated with Trileptal or placebo as adjunctive treatment and were numerically more common in the patients treated with any dose of Trileptal. Table 4 lists treatment-emergent signs and symptoms in patients converted from other AEDs to either high dose Trileptal or low dose (300 mg) Trileptal. 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 Treatment-Emergent Adverse Event Incidence in a Controlled Clinical Study of Adjunctive Therapy in Adults (Events in at Least 2% of Patients Treated with 2400 mg/day of Trileptal and Numerically More Frequent than in the Placebo Group)
|
Oxcarbazepine Dosage (mg/day) |
Body System/
Adverse Event |
OXC 600
N=163
% |
OXC 1200
N=171
% |
OXC 2400
N=126
% |
Placebo
N=166
% |
| 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 |
26 |
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 |
Table 4 Treatment-Emergent Adverse Event Incidence in Controlled Clinical Studies of Monotherapy in Adults Previously Treated with Other AEDs (Events in at Least 2% of Patients Treated with 2400 mg/day of Trileptal and Numerically More Frequent than in the Low Dose Control Group)
|
Oxcarbazepine Dosage (mg/day) |
Body System/
Adverse Event |
2400
N=86
% |
300
N=86
% |
| Body as a Whole |
|
|
| Fatigue |
21 |
5 |
| Fever |
3 |
0 |
| Allergy |
2 |
0 |
| Edema Generalized |
2 |
1 |
| Pain Chest |
2 |
0 |
| Digestive System |
|
|
| Nausea |
22 |
7 |
| Vomiting |
15 |
5 |
| Diarrhea |
7 |
5 |
| Dyspepsia |
6 |
|
