Lamictal (lamotrigine) Disease Interactions

Antiepileptic drugs can increase depression and suicidal thoughts or behaviors in patients receiving these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts and unusual changes in mood or behavior. Caregivers and family should be alert for the emergence or worsening of symptoms. Behaviors of concern should be reported immediately to the healthcare providers.

Severe, potentially fatal reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been associated with the use of lamotrigine. The incidence has been reported at approximately 1 in 1000 for adults and up to 1 in 50 for pediatric patients treated with the drug. Life-threatening rashes have usually, but not always, occurred within 2 to 8 weeks of initiating treatment. Therapy with lamotrigine should be administered cautiously in patients with preexisting drug-induced dermatitis, since it may delay the recognition of a potential reaction to lamotrigine. Lamotrigine therapy should be withdrawn promptly at the first sign of a rash. However, discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring. There have been suggestions that the risk of rash may be increased by 1) coadministration with valproic acid, 2) exceeding the recommended initial dosage, or 3) exceeding the recommended rate of dosage escalation of lamotrigine.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs across multiple indications in either monotherapy or adjunctive therapy for a median treatment duration of 12 weeks (up to a maximum of 24 weeks) showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. The estimated rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% for 16,029 placebo-treated patients, representing an increase of approximately one case for every 530 patients treated. There were four suicides in AED-treated patients and none in placebo-treated patients, although the number is too small to establish any causal relationship. The increased risk of suicidal thoughts or behavior was observed as early as one week after starting AEDs and persisted for the duration of treatment assessed. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Therapy with AEDs should be administered cautiously in patients with depression or other psychiatric disorders. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. For clinically significant or persistent symptoms, a dosage reduction or treatment withdrawal should be considered. If patients have symptoms of suicidal ideation or behavior, treatment should be discontinued.

Reports of blood dyscrasias that may or may not be associated with multi-organ hypersensitivity (also known as DRESS) have been reported in patients treated with lamotrigine. These have included neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, and, rarely, aplastic anemia and pure red cell aplasia.

Lamotrigine may slow ventricular conduction (widen QRS) and induce proarrhythmia in patients with structural heart disease or myocardial ischemia. In vitro studies have shown Class IB antiarrhythmic activity at therapeutically relevant concentrations. Clinical studies have not shown antiarrhythmic activity in healthy individuals, but because of the risk of proarrhythmia, including sudden death, lamotrigine should not be used in patients who have cardiac conduction disorders (e.g., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (e.g., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome or other sodium channelopathies).

Therapy with lamotrigine increases the risk of aseptic meningitis. Symptoms upon presentation included headache, fever, nausea, vomiting, and nuchal rigidity and usually occurred after treatment initiation. In most cases, symptoms resolved after discontinuation of treatment but returned quickly and more severely with reexposure. Some of the patients who developed aseptic meningitis had underlying diagnoses of systemic lupus erythematosus and other autoimmune diseases.

Lamotrigine is primarily converted by the liver to inactive glucuronide metabolites and subsequently eliminated by the kidney. Approximately 10% of a dose is excreted in the urine as unchanged drug. The plasma clearance of lamotrigine may be decreased and the half-life prolonged in patients with impaired renal and/or hepatic function. However, clinical data are limited. In a comparison of 12 healthy subjects and 24 with various degrees of liver disease, lamotrigine pharmacokinetics were significantly altered only in patients with severe cirrhosis. Therapy with lamotrigine should be administered cautiously and at reduced dosages in such patients.

Lamotrigine tablets for oral suspension (chewable dispersible tablets) contain phenylalanine. The phenylalanine content should be considered when these products are used in patients who must restrict their intake of phenylalanine (i.e. phenylketonurics).