Lamotrigine Side Effects: Common, Serious & FDA Warnings

Common Side Effects of Lamotrigine

The most-reported reactions in the FDA Adverse Event Reporting System (FAERS) for lamotrigine. Percentages reflect the share of reports mentioning each reaction; a single report may include multiple reactions. Reports indicate co-occurrence, not causation.

Serious Outcomes and FDA Warnings

FAERS reports flagged with a serious outcome (death, hospitalization, life-threatening, disability, or congenital anomaly), plus reactions surfaced in the FDA-approved label's Warnings section. Reports indicate co-occurrence, not causation.

From the FDA-approved label, Section 5.1: Serious Skin Rashes [see Boxed Warning] Pediatric

Population The incidence of serious rash associated with hospitalization and discontinuation of lamotrigine in a prospectively followed cohort of pediatric patients (aged 2 to 17 years) is approximately 0.3% to 0.8%. 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. Additionally, there have been rare cases of toxic epidermal necrolysis (TEN) with and without permanent sequelae and/or death in U.S. and foreign postmarketing experience.

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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 for epilepsy, 1.2% (6 of 482) experienced a serious rash compared with 0.6% (6 of 952) patients not taking valproate. Adult Population Serious rash associated with hospitalization and discontinuation of lamotrigine occurred in 0.3% (11 of 3,348) of adult patients who received lamotrigine in premarketing clinical trials of epilepsy. In the bipolar and other mood disorders clinical trials, the rate of serious rash was 0.08% (1 of 1,233) of adult patients who received lamotrigine as initial monotherapy and 0.13% (2 of 1,538) of adult patients who received lamotrigine as adjunctive therapy. No fatalities occurred among these individuals. However, 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, angioedema, and those associated with multi-organ hypersensitivity [ see Warnings and Precautions ( 5.3 )]. Risk Factors Concomitant Use of Valproate There is evidence that the inclusion of valproate in a multidrug regimen increases the risk of serious, potentially life-threatening rash in adults. Specifically, of 584 patients administered lamotrigine with valproate in epilepsy clinical trials, 6 (1%) were hospitalized in association with rash; in contrast, 4 (0.16%) of 2,398 clinical trial patients and volunteers administered lamotrigine in the absence of valproate were hospitalized. Patients with History of Allergy or Rash to Other Antiepileptic Drugs The risk of rash may be increased in patients with a history of allergy or rash to other AEDs. Not Adhering to the Recommended Dosage The risk of rash is increased by both exceeding the recommended initial dose of lamotrigine and exceeding the recommended dose escalation for lamotrigine. Patients with Genetic Variant Human Leukocyte Antigen (HLA)-B*1502 Allele Retrospective case-control studies in patients of certain Asian ancestry (e.g., Han Chinese and Thai) suggest that the HLA-B*1502 allele is associated with an increased risk (approximately 2 to 3 times higher) of developing Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in patients using lamotrigine. The risks and benefits of therapy should be weighed when considering use of lamotrigine in patients known to be positive for HLA-B*1502. Application of HLA genotyping as a screening tool has important limitations and must never substitute for appropriate clinical vigilance and patient management. Many HLA‑B*1502‑positive patients treated with lamotrigine will not develop SJS/TEN or other hypersensitivity reactions, and these reactions can still occur in HLA‑B*1502‑negative patients of any ethnicity.

From the FDA-approved label, Section 5.4: Cardiac Rhythm and Conduction

Abnormalities In vitro testing showed that lamotrigine exhibits Class IB antiarrhythmic activity at therapeutically relevant concentrations [see Clinical Pharmacology ( 12.2 )] . Based on these in vitro findings, lamotrigine could slow ventricular conduction (widen QRS) and induce proarrhythmia, which can lead to sudden death, in patients with clinically important structural or functional heart disease (i.e., patients with heart failure, valvular heart disease, congenital heart disease, conduction system disease, ventricular arrhythmias, cardiac channelopathies [e.g., Brugada syndrome], clinically important ischemic heart disease, or multiple risk factors for coronary artery disease).

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Any expected or observed benefit of lamotrigine in an individual patient with clinically important structural or functional heart disease must be carefully weighed against the risks for serious arrhythmias and/or death for that patient. Concomitant use of other sodium channel blockers may further increase the risk of proarrhythmia.

Lamotrigine Recalls

FDA enforcement actions matched to lamotrigine via openFDA's structured generic_name field and the NDC bridge. Ongoing recalls are listed below (verify on FDA →); closed recalls are grouped in the disclosure that follows.

No recalls are on record for this drug in the FDA enforcement database.

Lamotrigine Shortages

FDA-listed shortages of lamotrigine products. Strength and dosage-form level detail.

Is Lamotrigine Safe?

Lamotrigine is FDA-approved. The label's Warnings and Precautions section covers serious skin rashes [see boxed warning] pediatric (Section 5.1), hemophagocytic lymphohistiocytosis (Section 5.2), multiorgan hypersensitivity reactions and organ failure (Section 5.3), cardiac rhythm and conduction (Section 5.4), blood dyscrasias (Section 5.5), suicidal behavior and ideation (Section 5.6), aseptic meningitis (Section 5.7), potential medication errors (Section 5.8), concomitant use with estrogen-containing products, including oral contraceptives (Section 5.9), withdrawal seizures as with other (Section 5.10), status epilepticus (Section 5.11), addition of lamotrigine to a multidrug regimen that includes valproate (Section 5.12), binding in the eye and other melanin-containing tissues (Section 5.13), laboratory tests false-positive drug test results (Section 5.14).

As with any prescription, the assessment of safety is individual; consult a clinician about your own risk profile.

FDA-Approved Indications

Lamotrigine is FDA-approved for use in the condition categories below. The FDA-approved label’s Indications and Usage section is shown verbatim.

• Seizures
• Bipolar disorder

Lamotrigine orally disintegrating tablets are indicated for: Epilepsy—adjunctive therapy in patients aged 2 years and older : partial-onset seizures. primary generalized tonic-clonic (PGTC) seizures. generalized seizures of Lennox-Gastaut syndrome. ( 1.1 ) Epilepsy—monotherapy in patients aged 16 years and older : Conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug. ( 1.1 ) Bipolar disorder : Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy. ( 1.2 ) Limitations of Use: Treatment of acute manic or mixed episodes is not recommended.

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Effectiveness of lamotrigine in the acute treatment of mood episodes has not been established. 1.1 Epilepsy Adjunctive Therapy Lamotrigine orally disintegrating tablets are indicated as adjunctive therapy for the following seizure types in patients aged 2 years and older: partial-onset seizures. primary generalized tonic-clonic (PGTC) seizures. generalized seizures of Lennox-Gastaut syndrome. Monotherapy Lamotrigine orally disintegrating tablets are indicated for conversion to monotherapy in adults (aged 16 years and older) with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED). Safety and effectiveness of lamotrigine orally disintegrating tablets have not been established (1) as initial monotherapy; (2) for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate; or (3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs. 1.2 Bipolar Disorder Lamotrigine orally disintegrating tablets are indicated for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy [see Clinical Studies (14.2) ] . Limitations of Use Treatment of acute manic or mixed episodes is not recommended. Effectiveness of lamotrigine orally disintegrating tablets in the acute treatment of mood episodes has not been established.

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Data Sources & Methodology

How each section of this page is sourced, and how often the data is refreshed.

What we do not do. We do not invent, paraphrase, or extrapolate drug claims. Every figure on this page comes from a query against an openFDA endpoint. If the data is unavailable, the section gracefully omits rather than filling the space with editorial guesswork.