"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 more detail in the WARNINGS AND PRECAUTIONS section of the label:
- Serious skin rashes [see WARNINGS AND PRECAUTIONS]
- Multiorgan hypersensitivity reactions and organ failure [see WARNINGS AND PRECAUTIONS]
- Blood dyscrasias [see WARNINGS AND PRECAUTIONS]
- Suicidal behavior and ideation [see WARNINGS AND PRECAUTIONS]
- Aseptic meningitis [see WARNINGS AND PRECAUTIONS]
- Withdrawal seizures [see WARNINGS AND PRECAUTIONS]
- Status epilepticus [see WARNINGS AND PRECAUTIONS]
- Sudden unexplained death in epilepsy [see WARNINGS AND PRECAUTIONS]
Clinical Trial Experience With LAMICTAL XR For Treatment Of Primary Generalized Tonic-Clonic and Partial Onset Seizures
Most Common Adverse Reactions in Clinical Studies
Adjunctive Therapy in Patients With Epilepsy
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
LAMICTAL XR has been evaluated for safety in patients ≥ 13 years of age with PGTC and partial onset seizures. The most commonly observed adverse reactions in these 2 doubleblind, placebo-controlled trials of adjunctive therapy with LAMICTAL XR were, in order of decreasing incidence (treatment difference between LAMICTAL XR and placebo ≥ 4%): dizziness, tremor/intention tremor, vomiting, and diplopia.
In these 2 trials, adverse reactions led to withdrawal of 4 (2%) patients in the group receiving placebo and 10 (5%) patients in the group receiving LAMICTAL XR. Dizziness was the most common reason for withdrawal in the group receiving LAMICTAL XR (5 patients [3%]). The next most common adverse reactions leading to withdrawal in 2 patients each (1%) were rash, headache, nausea, and nystagmus. Table 4 displays the incidence of adverse reactions in these two 19-week, double-blind, placebo-controlled studies of patients with PGTC and partial onset seizures.
Table 4: Adverse Reaction Incidence in Double-Blind,
Placebo-Controlled Adjunctive Trials of Patients With Epilepsy (Adverse
Reactions ≥ 2% of Patients Treated With LAMICTAL XR and Numerically More
Frequent Than in the Placebo Group)
|Body System/Adverse Reaction||LAMICTAL XR
(n = 190) %
(n = 195) %
|Ear and labyrinth disorders|
|General disorders and administration site conditions|
|Asthenia and fatigue||6||4|
|Infections and infestations|
|Metabolic and nutritional disorders|
|Musculoskeletal and connective tissue disorder|
|Tremor and intention tremor||6||1|
|Cerebellar coordination and balance disorder||3||0|
|Respiratory, thoracic, and mediastinal disorders|
|Note: In these trials the incidence of nonserious rash was 2% for LAMICTAL XR and 3% for placebo. In clinical trials evaluating immediate-release lamotrigine, the rate of serious rash was 0.3% in adults on adjunctive therapy for epilepsy [see BOXED WARNING].|
Adverse reactions were also analyzed to assess the incidence of the onset of an event in the titration period, and in the maintenance period, and if adverse reactions occurring in the titration phase persisted in the maintenance phase.
The incidence for many adverse reactions caused by treatment with LAMICTAL XR was increased relative to placebo (i.e., treatment difference between LAMICTAL XR and placebo ≥ 2%) in either the titration or maintenance phases of the study. During the titration phase, an increased incidence (shown in descending order of % treatment difference) was observed for diarrhea, nausea, vomiting, somnolence, vertigo, myalgia, hot flush, and anxiety. During the maintenance phase, an increased incidence was observed for dizziness, tremor, and diplopia. Some adverse reactions developing in the titration phase were notable for persisting ( > 7 days) into the maintenance phase. These “persistent” adverse reactions included somnolence and dizziness.
There were inadequate data to evaluate the effect of dose and/or concentration on the incidence of adverse reactions because, although patients were randomized to different target doses based upon concomitant AED, the plasma exposure was expected to be generally similar among all patients receiving different doses. However, in a randomized, parallel study comparing placebo and 300 and 500 mg/day of immediate-release lamotrigine, the incidence of the most common adverse reactions ( ≥ 5%) such as ataxia, blurred vision, diplopia, and dizziness were dose related. Less common adverse reactions ( < 5%) were not assessed for dose-response relationships.
Monotherapy in Patients With Epilepsy
Adverse reactions observed in this study were generally similar to those observed and attributed to drug in adjunctive and monotherapy immediate-release lamotrigine and adjunctive LAMICTAL XR placebo-controlled studies. Only 2 adverse events, nasopharyngitis and upper respiratory tract infection, were observed at a rate of ≥ 3% and not reported at a similar rate in previous studies. Because this study did not include a placebo control group, causality could not be established [see Clinical Studies].
Other Adverse Reactions Observed During The Clinical Development Of immediate-Release Lamotrigine
All reported reactions are included except those already listed in the previous tables or elsewhere in the labeling, those too general to be informative, and those not reasonably associated with the use of the drug.
Adjunctive Therapy in Adults With Epilepsy
In addition to the adverse reactions reported above from the development of LAMICTAL XR, the following adverse reactions with an uncertain relationship to lamotrigine were reported during the clinical development of immediate-release lamotrigine for treatment of epilepsy in adults. These reactions occurred in ≥ 2% of patients receiving immediate-release lamotrigine and more frequently than in the placebo group.
Body as a Whole: Headache, flu syndrome, fever, neck pain.
Respiratory: Pharyngitis, cough increased.
Skin and Appendages: Rash, pruritus.
Monotherapy in Adults With Epilepsy
In addition to the adverse reactions reported above from the development of LAMICTAL XR, the following adverse reactions with an uncertain relationship to lamotrigine were reported during the clinical development of immediate-release lamotrigine for treatment of epilepsy in adults. These reactions occurred in > 2% of patients receiving immediate-release lamotrigine and more frequently than in the placebo group.
Body as a Whole: Chest pain.
Metabolic and Nutritional: Weight decrease, peripheral edema.
Nervous: Hypesthesia, libido increase, decreased reflexes.
Skin and Appendages: Contact dermatitis, dry skin, sweating.
Special Senses: Vision abnormality.
Urogenital (female patients only): Dysmenorrhea.
Other Clinical Trial Experience
Immediate-release lamotrigine has been administered to 6,694 individuals for whom complete adverse reaction data was captured during all clinical trials, only some of which were placebo controlled.
Adverse reactions are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse reactions are defined as those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare adverse reactions are those occurring in fewer than 1/1,000 patients.
Hematologic and Lymphatic System: Infrequent: Ecchymosis, leukopenia. Rare: Anemia, eosinophilia, fibrin decrease, fibrinogen decrease, iron deficiency anemia, leukocytosis, lymphocytosis, macrocytic anemia, petechia, thrombocytopenia.
Metabolic and Nutritional Disorders: Infrequent: Aspartate transaminase increased. Rare: Alcohol intolerance, alkaline phosphatase increase, alanine transaminase increase, bilirubinemia, gamma glutamyl transpeptidase increase, hyperglycemia.
Musculoskeletal System: Rare: Muscle atrophy, pathological fracture, tendinous contracture.
Nervous System: Frequent: Confusion. Infrequent: Akathisia, apathy, aphasia, depersonalization, dysarthria, dyskinesia, euphoria, hallucinations, hostility, hyperkinesia, hypertonia, libido decreased, memory decrease, mind racing, movement disorder, myoclonus, panic attack, paranoid reaction, personality disorder, psychosis, stupor. Rare: Choreoathetosis, delirium, delusions, dysphoria, dystonia, extrapyramidal syndrome, hemiplegia, hyperalgesia, hyperesthesia, hypokinesia, hypotonia, manic depression reaction, neuralgia, paralysis, peripheral neuritis.
Respiratory System: Rare: Hiccup, hyperventilation.
Special Senses: Frequent: Amblyopia. Infrequent: Abnormality of accommodation, conjunctivitis, dry eyes, ear pain, photophobia, taste perversion, tinnitus. Rare: Deafness, lacrimation disorder, oscillopsia, parosmia, ptosis, strabismus, taste loss, uveitis, visual field defect.
Urogenital System: Infrequent: Abnormal ejaculation, hematuria, impotence, menorrhagia, polyuria, urinary incontinence. Rare: Acute kidney failure, breast neoplasm, creatinine increase, female lactation, kidney failure, kidney pain, nocturia, urinary retention, urinary urgency.
Postmarketing Experience With Immediate-Release Lamotrigine
The following adverse events (not listed above in clinical trials or other sections of the prescribing information) have been identified during postapproval use of immediate-release lamotrigine. Because these events 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.
Hepatobiliary Tract and Pancreas: Pancreatitis.
Lower Respiratory: Apnea.
Musculoskeletal: Rhabdomyolysis has been observed in patients experiencing hypersensitivity reactions.
Non-site Specific: Progressive immunosuppression.
Read the Lamictal XR (lamotrigine extended-release tablets) Side Effects Center for a complete guide to possible side effects
Significant drug interactions with lamotrigine are summarized in Table 5. Additional details of these drug interaction studies, which were conducted using immediate-release lamotrigine, are provided in the Clinical Pharmacology section [see CLINICAL PHARMACOLOGY].
Table 5: Established and Other Potentially Significant
|Concomitant Drug||Effect on Concentration of Lamotrigine or Concomitant Drug||Clinical Comment|
|Estrogen-containing oral contraceptive preparations containing 30 mcg ethinylestradiol and 150 mcg levonorgestrel||↓ lamotrigine
|Decreased lamotrigine levels approximately 50%.
Decrease in levonorgestrel component by 19%.
|Carbamazepine and carbamazepine epoxide||↓ lamotrigine
? CBZ epoxide
|Addition of carbamazepine decreases lamotrigine concentration approximately 40%.
May increase carbamazepine epoxide levels.
|Phenobarbital/Primidone||↓ lamotrigine||Decreased lamotrigine concentration approximately 40%.|
|Phenytoin||↓ lamotrigine||Decreased lamotrigine concentration approximately 40%.|
|Rifampin||↓ lamotrigine||Decreased lamotrigine AUC approximately 40%.|
|Increased lamotrigine concentrations slightly more than 2-fold.
Decreased valproate concentrations an average of 25% over a 3-week period then stabilized in healthy volunteers; no change in controlled clinical trials in epilepsy patients.
|↓ = Decreased (induces lamotrigine
↑ = Increased (inhibits lamotrigine glucuronidation).
?= Conflicting data.
Read the Lamictal XR Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 1/27/2014
This monograph has been modified to include the generic and brand name in many instances.
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