The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0. In a prospectively followed cohort of 1, pediatric patients aged 2 to 16 years with epilepsy taking adjunctive immediate-release lamotrigine, there was 1 rash-related death. However, cases have occurred in the absence of these factors. Nearly all cases of life-threatening rashes caused by immediate-release lamotrigine have occurred within 2 to 8 weeks of treatment initiation, information about lamictal.
However, isolated cases have occurred after prolonged treatment e. Accordingly, duration of therapy cannot be relied upon as means to predict the potential risk heralded by the first appearance of a rash.
Lamotrigine is a white to pale cream-colored powder and has a pKa of 5. Lamotrigine is very slightly soluble in water 0. The structural formula is:. Each tablet contains the labeled amount of lamotrigine and the following inactive ingredients: Tablets are printed with edible black ink. The combination of this and the modified-release core are designed to control the dissolution rate of lamotrigine over a period of approximately 12 to 15 hours, leading to a gradual increase in serum lamotrigine levels.
Tablets must be swallowed whole and must not be chewed, crushed, or information about lamictal. Therefore, it is important that the dosing recommendations be followed closely. It is recommended that LAMICTAL XR not be restarted in patients who discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefits clearly outweigh the risks.
The greater the interval of time since the previous dose, the greater consideration should be given to restarting with the initial dosing recommendations.
If a patient has discontinued lamotrigine for a period of more than 5 half-lives, it is recommended that initial dosing recommendations and guidelines be followed. Because lamotrigine is metabolized predominantly by glucuronic acid conjugation, drugs that are known to induce or inhibit glucuronidation may affect the apparent clearance of lamotrigine.
A therapeutic information about lamictal concentration range has not been established for lamotrigine. The effect of other hormonal contraceptive preparations or hormone replacement therapy on the pharmacokinetics of lamotrigine has not been systematically evaluated. It has been reported that ethinylestradiol, not progestogens, increased the clearance of lamotrigine up to 2-fold, and the progestin -only pills had no effect on lamotrigine plasma levels. Experience in patients with hepatic impairment is limited.
No dosage adjustment is needed in patients with mild liver impairment. Escalation and maintenance doses may be adjusted according to clinical response, information about lamictal. Few patients with severe renal impairment have been evaluated during chronic treatment with immediate-release lamotrigine. This section provides specific dosing recommendations for patients aged 13 years and older. Specific dosing recommendations are provided depending upon concomitant AEDs or other concomitant medications.
The regimen for the withdrawal of the concomitant AED is based on experience gained in the controlled monotherapy clinical trial using immediate-release lamotrigine. Maintain established stable dose. Depending on the therapeutic response after conversion, information about lamictal, the total daily dose may need to be adjusted within the recommended dosing instructions Table 1.
Adjunctive Therapy in Patients With Epilepsy: Because clinical trials are conducted under widely varying conditions, information about lamictal, 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.
Table 4 displays the incidence of adverse reactions in these two week, double-blind, placebo-controlled trials of patients with PGTC and partial information about lamictal seizures. In clinical trials evaluating immediate-release lamotrigine, the rate of serious rash was 0. 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.
During the maintenance phase, information about lamictal increased incidence was observed for dizziness, tremorinformation about lamictal, and diplopia. These persistent adverse reactions included somnolence and dizziness, information about lamictal. Monotherapy in Patients With Epilepsy: Adverse reactions observed in this trial were generally similar to those observed and attributed to drug in adjunctive and monotherapy immediate-release lamotrigine and adjunctive LAMICTAL XR placebo-controlled trials.
Because this trial did not include a placebo control group, causality could not be established [see Clinical Studies ]. 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. 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 liver disease accutane. Information about lamictal, convulsionirritability, speech disorderconcentration disturbance.
Pharyngitiscough increased. Urogenital female patients only: Vaginitisamenorrheadysmenorrhea. Rectal hemorrhagepeptic ulcer. Hypesthesia, libido increase, decreased reflexes.
Contact dermatitisdry skin, sweating. Immediate-release lamotrigine has been administered to 6, 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: Hypertensionpalpitationspostural hypotensionsyncopetachycardiavasodilation.
Acne, alopeciahirsutismmaculopapular rash, urticaria. Leukoderma, multiforme erythemapetechial rash, pustular rash. Dysphagiainformation about lamictal, liver function tests abnormal, mouth ulceration. Gastrointestinal hemorrhage, hemorrhagic colitishepatitismelena and stomach ulcer.
Hematologic and Lymphatic System: Anemiaeosinophiliafibrin decrease, fibrinogen decrease, iron deficiency anemialeukocytosisinformation about lamictal, lymphocytosismacrocytic anemia, petechia, thrombocytopenia. Metabolic and Nutritional Disorders: Alcohol intolerance, alkaline phosphatase increase, alanine transaminase increase, bilirubinemia, gamma glutamyl transpeptidase increase, information about lamictal. Muscle atrophypathological fracture, tendinous contracture.
Akathisiainformation about lamictal, aphasiadepersonalization, dysarthriadyskinesiaeuphoriainformation about lamictal, hallucinations, hostility, hyperkinesia, information about lamictal, hypertonialibido decreased, memory decrease, mind racing, movement information about lamictal, myoclonuspanic attack, paranoid reaction, personality disorder, psychosisstupor. Choreoathetosis, deliriumdelusions, dysphoriadystoniaextrapyramidal syndrome, hemiplegiahyperalgesia, hyperesthesia, hypokinesia, hypotoniamanic depression reaction, neuralgiaparalysisperipheral neuritis.
Abnormality of accommodationconjunctivitisinformation about lamictal eyes, ear pain, photophobiataste perversion, tinnitus. Deafness, lacrimation disorder, oscillopsiaparosmia, ptosisstrabismustaste loss, information about lamictal, uveitisvisual field defect. Abnormal ejaculationhematuriaimpotencemenorrhagiapolyuriaurinary incontinence. Acute kidney failure, breast neoplasmcreatinine increase, female lactation, kidney failure, kidney pain, nocturiaurinary retention, urinary urgency.
The following adverse events not listed above in clinical actress yasmin bleeth photo gallery 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 hot issue about cancer estimate their frequency or establish a causal relationship to drug exposure. Agranulocytosishemolytic anemialymphadenopathy not associated with hypersensitivity disorder.
Lupus -like reaction, vasculitis. Rhabdomyolysis has been observed in patients experiencing hypersensitivity reactions. Significant drug interactions with lamotrigine are summarized in this section. May increase carbamazepine epoxide levels. There are conflicting study results regarding effect of lamotrigine on valproate concentrations: This may result in increased plasma levels of certain drugs that are substantially excreted via this route, information about lamictal.
The incidence of serious rash associated with hospitalization and discontinuation of immediate-release lamotrigine in a prospectively followed cohort of pediatric patients aged 2 to 16 years with epilepsy receiving adjunctive therapy with immediate-release lamotrigine was approximately 0, information about lamictal. When 14 of these cases were reviewed by 3 expert dermatologists, there was considerable disagreement as to their proper classification.
To illustrate, one dermatologist considered none of the cases to be Stevens-Johnson syndrome ; another assigned 7 of the 14 to this diagnosis. There information about lamictal 1 rash-related death in this 1,patient cohort. There is evidence that the inclusion of valproate in a multidrug regimen increases the risk of serious, potentially life-threatening rash in pediatric patients.
In pediatric patients who used valproate concomitantly, 1. Serious rash associated with hospitalization and discontinuation of immediate-release lamotrigine national action plans bologna in 0.
In worldwide postmarketing experience, rare cases of rash-related death have been reported, but their numbers are too few to permit a precise estimate of the rate. Among the rashes leading to hospitalization were Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedemaand those associated with multiorgan hypersensitivity [see Multiorgan Hypersensitivity Reactions and Organ Failure ].
There is evidence that the inclusion of valproate in a multidrug regimen increases the risk of serious, potentially life-threatening rash in adults, information about lamictal. Multiorgan hypersensitivity reactions, also known as drug reaction with eosinophilia and systemic symptoms DRESShave occurred with lamotrigine. Some have been fatal or life threatening. Eosinophilia is often present.
This disorder is variable in its expression and other organ systems not noted here may be involved. Fatalities associated with acute amino acids therapy plans failure and various degrees of hepatic failure have been reported in 2 of 3, adult patients and 4 of 2, pediatric patients who received lamotrigine in epilepsy clinical trials.
Rare fatalities from multiorgan failure have also been reported in postmarketing use. Isolated liver failure without rash or involvement of other organs has also been reported with lamotrigine. It is important to note that early manifestations of hypersensitivity e.
If such signs or symptoms are present, the patient should be evaluated immediately. There have been reports of blood dyscrasias with immediate-release lamotrigine that may or may not be associated with multiorgan hypersensitivity also known as DRESS [see Multiorgan Hypersensitivity Reactions and Organ Failure ].
These have included neutropenialeukopeniaanemiathrombocytopeniapancytopeniaand, rarely, aplastic anemia and pure red cell aplasia. Pooled analyses of placebo-controlled clinical trials monotherapy and adjunctive therapy of 11 different AEDs showed that patients randomized to 1 of the AEDs had approximately twice the risk adjusted Relative Risk 1. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence of suicidal behavior or ideation among 27, AED-treated patients was 0.