A patient taking lamotrigine 25 mg has developed a small rash in the axilla; what management steps should be taken?

Discontinue lamotrigine immediately—any rash at any dose is a potential harbinger of Stevens-Johnson syndrome or toxic epidermal necrolysis, and continuing the drug risks life-threatening outcomes.

Immediate Action Required

Stop lamotrigine now and do not administer another dose. 1 The appearance of any rash during lamotrigine therapy mandates immediate discontinuation, as this is the single most critical intervention to prevent progression to severe cutaneous adverse reactions that carry significant morbidity and mortality. 1

Clinical Assessment of the Rash

Examine the patient urgently for features that distinguish benign from serious rash:

• Check for mucosal involvement (oral, ocular, genital lesions)—any mucosal findings indicate a severe reaction and absolute contraindication to future lamotrigine use. 2
• Assess for systemic symptoms: fever, lymphadenopathy, facial swelling, or constitutional symptoms (malaise, arthralgias) suggest DRESS syndrome or Stevens-Johnson syndrome. 2
• Document rash characteristics: distribution (localized axillary vs. widespread), morphology (maculopapular vs. vesiculobullous), and timing relative to drug initiation. 3

In this case, a "small rash on the armpits" at 25 mg suggests early presentation during the initiation phase—12 of 13 allergic reactions in one series occurred during initiation. 3

Why This Dose and Location Do Not Reduce Risk

• The 25 mg starting dose does not protect against rash if titration was too rapid or if the patient has individual susceptibility. 1, 3
• Localized distribution (axillae only) does not predict benign course—rashes can progress rapidly from limited to widespread involvement within days. 4
• Even patients maintained on lamotrigine for years can develop rash, so duration of prior tolerance is not protective. 5

Risk Factors Present in This Case

• Rapid dose escalation beyond recommended 2-week intervals is a major risk factor for serious rash. 1
• If the patient is co-prescribed valproic acid, the risk of rash increases substantially (9.1% vs. 2.8% with enzyme-inducers). 3
• Exceeding recommended initial dosage is another established risk factor. 6

Management After Discontinuation

• Provide supportive care with moderate-to-high-potency topical corticosteroids (e.g., mometasone furoate 0.1% or betamethasone valerate 0.1%) for symptomatic relief of localized rash. 2
• Monitor closely for progression over the next 48–72 hours; instruct the patient to return immediately if the rash spreads, blisters develop, or systemic symptoms appear. 2
• Document the reaction in the medical record and inform the patient that lamotrigine is contraindicated in the future. 1

Rechallenge: Almost Always Contraindicated

Do not rechallenge with lamotrigine. 1 Both the American College of Clinical Pharmacology and consensus guidelines state that previous lamotrigine-induced rash is an absolute contraindication to restarting the drug. 1

• Rechallenge should be considered only if the rash was definitively mild, non-serious, lamotrigine was uniquely effective for a severe psychiatric condition with no alternatives, and the patient had been on lamotrigine for >6 months previously. 2
• Any mucosal involvement is an absolute contraindication to rechallenge. 2
• If rechallenge is attempted (rarely justified), it must use an ultra-slow titration starting at 0.1 mg/day, not the standard 25 mg dose. 7

In this case, the patient has only been on 25 mg (early initiation phase), so rechallenge criteria are not met. 2

Alternative Treatment Options

• For bipolar disorder or mood stabilization: consider lithium, valproic acid (if not a woman of childbearing potential), or atypical antipsychotics. 6
• For neuropathic pain: gabapentin or pregabalin are evidence-based alternatives. 2
• For anxiety: SSRIs, SNRIs, or buspirone are appropriate pharmacologic options. 2
• For epilepsy: levetiracetam, carbamazepine, or other antiepileptic drugs depending on seizure type. 6

Common Pitfalls to Avoid

• Do not "watch and wait" with continued lamotrigine dosing—even mild rashes can progress to Stevens-Johnson syndrome within days. 4
• Do not assume localized rash is benign—distribution does not predict severity. 4
• Do not restart lamotrigine at the previous dose if rechallenge is ever considered in the future; full re-titration from ultra-low doses is mandatory. 2
• Do not underestimate the risk in patients without valproic acid—serious reactions occur in monotherapy and with other co-medications. 4