"The U.S. Food and Drug Administration today approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat seizures associated with epilepsy.
Epilepsy is a brain disorder caused by abnormal or excessive activity in the brain"...
The following adverse reactions are described in other sections of the labeling:
- Hyponatremia [see WARNINGS AND PRECAUTIONS]
- Anaphylactic Reactions and Angioedema [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity Reactions in Patients with Hypersensitivity to Carbamazepine [see WARNINGS AND PRECAUTIONS]
- Serious Dermatological Reactions [see WARNINGS AND PRECAUTIONS]
- Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]
- Withdrawal of AEDs [see WARNINGS AND PRECAUTIONS]
- Multi-Organ Hypersensitivity [see WARNINGS AND PRECAUTIONS]
- Hematologic Reactions [see WARNINGS AND PRECAUTIONS]
- Risk of Seizures in the Pregnant Patient [see WARNINGS AND PRECAUTIONS]
- Laboratory Tests [see WARNINGS AND PRECAUTIONS]
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 epilepsy who received Oxtellar XR™ (366 adults and 18 children) 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 children.
Most Common Adverse Reactions Reported by Adult Patients Receiving Concomitant AEDs in Oxtellar XR™ Clinical Studies
Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with Oxtellar XR™ or placebo and concomitant AEDs and that were numerically more common in the patients treated with any dose of Oxtellar XR™ than in patients receiving placebo.
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 Oxtellar XR™ and more frequent than in placebo-treated patients were: dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, and asthenia.
Table 3: Adverse Reaction Incidence in a Controlled Clinical Study
of Oxtellar XR™ with Concomitant AEDs in Adults*
|Oxtellar XR 2400 mg/day
|Oxtellar XR 1200 mg/day
|Any System / Any Term||69||57||55|
|Nervous System Disorders|
|Abdominal Pain Upper||0||3||1|
|General Disorders And Administration Site Conditions|
|Infections And Infestations|
|* Reported by ≥ 2% of Patients Treated with Oxtellar XR™ and Numerically More Frequent than in the Placebo Group|
Adverse Reactions Associated with Discontinuation of Oxtellar XR™ Treatment
Approximately 23.3% of the 366 adult patients receiving Oxtellar XR™ in clinical studies discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation of Oxtellar XR™ (reported by ≥ 2%) were: dizziness (9.8%), vomiting (5.3%), nausea (3.7%), diplopia (3.2%), and somnolence (2.4%).
Adjunctive Therapy with Oxtellar XR™ in Pediatric Patients 4 to 16 Years Old Previously Treated with other AEDs
In a pharmacokinetic study in 18 children (age 4-16 years) with partial seizures treated with different doses of Oxtellar XR™, the observed adverse reactions seen in association with Oxtellar XR™ 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 dose of immediate-release oxcarbazepine than in placebo. As immediate-release oxcarbazepine and Oxtellar XR™ 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 %
N = 163 %
N = 171 %
N = 126 %
|Body as a Whole|
|Metabolic and Nutritional Disorders|
|Sprains and Strains||0||2||2||1|
|Cranial Injury NOS||1||0||2||1|
|Skin and Appendages|
|* Events in at Least 2% of Patients Treated with 2400mg/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.
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.
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.
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.
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.
Postmarketing and Other Experience
The following adverse reactions have been identified during post-approval use of immediate-release 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]
Anaphylaxis: [see WARNINGS AND PRECAUTIONS]
Read the Oxtellar XR (oxcarbazepine extended-release tablets) Side Effects Center for a complete guide to possible side effects
Oxcarbazepine and MHD induce a subgroup of the cytochrome P450 3A family (CYP3A4 and CYP3A5).
In addition, several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD.
These interactions have implications when Oxtellar XR™ is used with other AEDs or hormonal contraceptives.
Other Antiepileptic Drugs
Potential interactions between immediate-release oxcarbazepine and other AEDs were assessed in clinical studies. Oxtellar XR™ would be expected to have the same effects on coadministered AEDs as immediate-release oxcarbazepine.
Table 5: AED Drug Interactions with Oxcarbazepine
|AED Coadministered (daily dose)||IR- Oxcarbazepine (daily dose)||Influence of IR-Oxcarbazepine on AED Concentration Mean Change [90% Confidence Interval]||Influence of AED on MHD Concentration (Mean Change, 90% Confidence Interval)||Recommendation|
|Carbamazepine (400 - 2000 mg)||900 mg||nc1||40% decrease
[CI: 17% decrease, 57% decrease]
|Consider initiating Oxtellar XR™ at a higher dose. Monitor and titrate dose to desired clinical effect (see DOSAGE AND ADMINISTRATION)|
|Phenobarbital (100 - 150 mg)||600 - 1800 mg||14% increase
[CI: 2%increase, 24% increase]
[CI: 12% decrease, 51% decrease]
|Phenytoin (250 - 500 mg)||600 - 1800
|nc1,2 up to 40% increase3
[CI: 12% increase, 60% increase]
[CI: 3% decrease, 48% decrease]
|Valproic Acid (400 - 2800 mg)||600-1800||nc1||18% decrease
[CI: 13% decrease, 40% decrease]
|Monitor. Dose adjustment of Oxtellar XR™ may not be needed.|
|1nc denotes a mean change of less than 10%
3Mean increase in adults at high doses of immediate-release oxcarbazepine
Coadministration of immediate-release oxcarbazepine with an oral contraceptive decreased the plasma concentrations of two components of hormonal contraceptives, ethinylestradiol and levonorgestrel. Therefore, concurrent use of Oxtellar XR™ with these hormonal contraceptives and other oral or implant contraceptives may render these contraceptives less effective [see CLINICAL PHARMACOLOGY]. Additional non-hormonal forms of contraception are recommended.
Drug Abuse And Dependence
The abuse potential of Oxtellar XR™ has not been evaluated in human studies. Oxtellar XR™ is not habit forming, and is not expected to encourage abuse.
Intragastric injections of oxcarbazepine to four cynomolgus monkeys demonstrated no signs of physical dependence as measured by the desire to self-administer oxcarbazepine by lever pressing activity.
Last reviewed on RxList: 11/9/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Oxtellar XR Information
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