WARNING: SERIOUS SKIN RASHES.
LAMLIQUE can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.3% to 0.8% in pediatric patients (aged 2 to 17 years) and 0.08% to 0.3% in adults receiving lamotrigine. One rash-related death was reported in a prospectively followed cohort of 1,983 pediatric patients (aged 2 to 16 years) with epilepsy taking lamotrigine as adjunctive therapy. In worldwide postmarketing experience, rare cases of toxic epidermal necrolysis and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate.
In addition to age, factors that may increase the risk of occurrence or the severity of rash caused by lamotrigine include (1) coadministration of lamotrigine with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of lamotrigine, (3) exceeding the recommended dose escalation for lamotrigine, or (4) the presence of the HLA-B*1502 allele. However, cases have occurred in the absence of these factors.
Nearly all cases of life-threatening rashes caused by lamotrigine have occurred within 2 to 8 weeks of treatment initiation. However, isolated cases have occurred after prolonged treatment (e.g., 6 months). Accordingly, duration of therapy cannot be relied upon as means to predict the potential risk heralded by the first appearance of a rash.
Although benign rashes are also caused by lamotrigine, it is not possible to predict reliably which rashes will prove to be serious or life threatening. Accordingly, LAMLIQUE should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug related. Discontinuation of treatment may not prevent a rash from becoming life threatening or permanently disabling or disfiguring.
Serious Skin Rashes[see Boxed Warning]: Serious rashes associated with hospitalization and discontinuation of lamotrigine have occurred. Risk factors that may increase the risk of occurrence or severity of rash include (1) coadministration of lamotrigine with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of lamotrigine, (3) exceeding the recommended dose escalation for lamotrigine, or (4) the presence of the HLA-B*1502 allele. The risk of rash may also be increased in patients with a history of allergy or rash to other antiepileptic drugs. Discontinue LAMLIQUE at the first sign of rash, unless the rash is clearly not drug related.
Hemophagocytic Lymphohistiocytosis (HLH): HLH, a life-threatening syndrome of pathologic immune activation, has occurred in pediatric and adult patients taking lamotrigine. Reported symptoms have occurred within 8 to 24 days following initiation of treatment. Evaluate patients immediately for manifestations of systemic inflammation, including fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, high serum ferritin, hypertriglyceridemia, and liver-function or coagulation abnormalities. Discontinue LAMLIQUE if an alternative etiology cannot be established.
Fatal or Life-Threatening Multiorgan Hypersensitivity Reactions and Organ Failure (DRESS): Multiorgan hypersensitivity (DRESS) have occurred with patients taking antiepileptic drugs, including lamotrigine. DRESS can be fatal or life threatening and may present with fever, rash, lymphadenopathy and/or facial swelling in association with other organ system involvement, sometimes resembling an acute viral infection. Eosinophilia is often present. Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may occur without rash. Evaluate immediately and discontinue LAMLIQUE if an alternative etiology cannot be established.
Cardiac Rhythm and Conduction Abnormalities: In vitro findings indicate that LAMLIQUE could cause serious and potentially life-threatening cardiac rhythm and conduction abnormalities, particularly in patients with underlying cardiac disorders or arrhythmias. In patients with clinically important structural or functional heart disease, carefully weigh the expected benefit of treatment against the risk. Discontinue LAMLIQUE if excessive depression of cardiac conduction or significant arrhythmias occur. Concomitant use of other sodium channel blockers may further increase risk of proarrhythmia.
Blood Dyscrasias: Neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, and, rarely, aplastic anemia and pure red cell aplasia have been reported, with or without association with multiorgan hypersensitivity (DRESS).
Suicidal Behavior and Ideation: Antiepileptic drugs, including LAMLIQUE, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients for the emergence or worsening depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Inform patients, caregivers, and families of this risk and advise them to report behaviors of concern immediately to healthcare providers.
Aseptic Meningitis: LAMLIQUE increases the risk of developing aseptic meningitis. Symptoms upon presentation have included headache, fever, nausea, vomiting, nuchal rigidity, rash, photophobia, myalgia, chills, altered consciousness, and somnolence. Symptoms have been reported to resolve after discontinuation of lamotrigine. Monitor for signs of meningitis, evaluate patients for other causes, and treat as appropriate.
Potential Medication Errors: Medication errors involving lamotrigine have occurred due to confusion with the names of other commonly used medications and between different formulations of lamotrigine. Clearly write and say LAMLIQUE and the concentration per mL. Strongly advise patients to visually inspect the product and verify they received LAMLIQUE oral suspension and the correct strength each time they fill their prescription.
Concomitant Use with Estrogen-Containing Products, Including Oral Contraceptives: Estrogen-containing oral contraceptives can decrease lamotrigine serum concentrations. Dosage adjustments will be necessary in most patients who start or stop them while taking LAMLIQUE. During the week of inactive hormonal preparation (pill-free week), plasma lamotrigine levels are expected to rise, as much as doubling at the end of the week. Adverse reactions consistent with elevated levels of lamotrigine, such as dizziness, ataxia, and diplopia, could occur.
Withdrawal Seizures: LAMLIQUE should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. The dosage of LAMLIQUE should be tapered over a period of at least 2 weeks (approximately 50% reduction per week), unless rapid discontinuation is required for a serious adverse reaction.
Status Epilepticus: Treatment-emergent status epilepticus and variably defined episodes of seizure exacerbation have been reported, although valid estimates of the incidence are difficult to obtain.
Binding in the Eye and Other Melanin-Containing Tissues: Lamotrigine binds to melanin and could accumulate in melanin-rich tissues over time, potentially causing toxicity after extended use. Prescribers should be aware of the possibility of long-term ophthalmologic effects.
False-Positive Drug Test Results: Lamotrigine can interfere with some rapid urine drug screens and cause false-positive readings, particularly for phencyclidine (PCP).
