How should Stevens‑Johnson syndrome caused by Vimpat (lacosamide) be managed, and what alternative antiepileptic drugs are recommended?

Management of Vimpat (Lacosamide)-Induced Stevens-Johnson Syndrome

Immediately discontinue Vimpat (lacosamide) at the first sign of rash or mucosal involvement, as this is the single most critical intervention to reduce mortality. 1, 2

Immediate Actions Upon Diagnosis

• Stop lacosamide permanently and document this as an allergy in all medical systems, flagging it prominently in the patient's medical record 1, 2
• Calculate SCORTEN within the first 24 hours of admission using 7 clinical parameters (age, BSA involvement, heart rate, serum glucose, bicarbonate, BUN, presence of malignancy) to predict mortality risk 2
• Transfer patients with >10% body surface area (BSA) epidermal loss immediately to a burn center or ICU experienced in managing extensive skin loss, as delayed transfer increases mortality 2
• Document all medications taken in the prior 2 months, including over-the-counter preparations, to identify any additional potential causative agents 2
• Report the adverse reaction to pharmacovigilance authorities (MHRA in the U.K., MedWatch in the U.S.) 3, 1

Critical Supportive Care Management

Fluid and Wound Management

• Initiate fluid replacement using the formula: body weight (kg) × % BSA epidermal detachment = mL/hour, which is significantly less aggressive than burn formulas to avoid fluid overload 2
• Cleanse wounds regularly with warmed sterile water, saline, or chlorhexidine (1:5000) 3, 2
• Apply greasy emollients (50% white soft paraffin with 50% liquid paraffin) over all skin, including denuded areas; consider aerosolized formulations to minimize shearing forces 3, 2
• Apply nonadherent dressings (Mepitel™ or Telfa™) to denuded dermis with secondary foam dressings to collect exudate 3
• Avoid prophylactic systemic antibiotics; only institute antimicrobial therapy if clinical signs of infection develop (confusion, hypotension, reduced urine output, oxygen desaturation, increased skin pain) 2

Nutritional Support

• Provide continuous enteral nutrition via oral route or nasogastric tube if oral intake is precluded by buccal mucositis 3, 2
• Deliver 20-25 kcal/kg daily during the early catabolic phase, increasing to 25-30 kcal/kg daily during the anabolic recovery phase 3, 2

Pain Management

• Use the WHO analgesic ladder approach, providing adequate background simple analgesia to ensure comfort at rest 3, 2
• Provide additional breakthrough analgesia for dressing changes and procedures 3

Systemic Immunomodulatory Therapy

For Grade 3-4 SJS/TEN, first-line systemic treatment is IV methylprednisolone 0.5-1 mg/kg for Grade 3, or 1-2 mg/kg for Grade 4, tapering when toxicity resolves. 2 This recommendation reflects the most recent guideline consensus, though the evidence remains controversial 3, 4, 5

• High-dose IVIG (2-3 g/kg over 3-5 days, typically 1 g/kg/day for 3 days) may be added in severe or steroid-unresponsive cases 3, 2
• Cyclosporine (3 mg/kg for 14 days, tapered by 10 mg daily for 2 weeks) is an alternative immunomodulatory option with emerging evidence of mortality benefit 3, 4
• TNF-α inhibitors show increasing evidence of decreased mortality in SJS/TEN 4, 5

Specialized Organ System Management

Ophthalmologic Care

• Obtain ophthalmology consultation immediately, as 74% of SJS/TEN patients develop acute ocular involvement 2
• 50-63% of patients with acute involvement develop chronic complications (severe dry eyes, trichiasis, corneal scarring) 2
• Early ophthalmologic intervention can prevent long-term visual impairment 3

Oral and Mucosal Care

• Clean the mouth daily with warm saline mouthwashes or oral sponges, sweeping gently in labial and buccal sulci to reduce fibrotic scar risk 3
• Use benzydamine hydrochloride oral rinse or spray every 3 hours, particularly before eating 3
• Apply antiseptic oral rinse (1.5% hydrogen peroxide or 0.2% chlorhexidine digluconate) twice daily to reduce bacterial colonization 3
• Consider topical corticosteroid (betamethasone sodium phosphate 0.5 mg in 10 mL water as rinse-and-spit) four times daily 3

Urogenital Care

• Examine the urogenital tract as part of initial assessment; obtain early vulval specialist consultation in women for consideration of dilators to prevent vaginal synechiae 3
• Apply white soft paraffin ointment to urogenital skin and mucosae every 4 hours 3
• Use Mepitel dressings to eroded areas; insert dilator or tampon wrapped in Mepitel into vagina to prevent synechiae formation 3
• Catheterize all patients to prevent urethral strictures 3

Alternative Antiepileptic Drug Selection

Avoid all aromatic antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, lamotrigine) due to cross-reactivity risk. 1, 6, 7

Safer Alternative AEDs for Lacosamide

• Levetiracetam is a preferred alternative as it is structurally unrelated to aromatic AEDs and has a lower risk profile for severe cutaneous reactions 7
• Valproic acid may be considered, though caution is warranted as polytherapy increases adverse effect frequency 6
• Gabapentin or pregabalin are additional options with lower SJS/TEN risk 7
• Topiramate is another structurally distinct alternative with lower severe cutaneous reaction risk 7

Critical Pitfalls to Avoid

• Do not rechallenge with lacosamide or any drug within the same chemical class, as re-exposure is likely to elicit a new episode of increased severity 3, 7
• Do not use prophylactic antibiotics indiscriminately, as this increases Candida colonization and promotes resistant organisms 2
• Do not delay transfer to specialized care, as this is associated with increased mortality 2
• Do not underestimate fluid requirements but avoid overaggressive resuscitation using burn formulas 2

Discharge Planning and Long-Term Follow-Up

• Provide written information about lacosamide and any related medications to avoid permanently 3
• Advise patients to wear a MedicAlert bracelet indicating lacosamide allergy 1
• Warn patients and families about expected fatigue and lethargy for several weeks following discharge 3
• Arrange follow-up with ophthalmology, dermatology, and other specialists as needed for monitoring of chronic complications (ocular damage, oral/genital scarring) 3
• Refer to local social services for needs assessment and support groups (SJS Awareness U.K. or equivalent) 3