Cross-sensitivity of skin rashes with antiepileptic drug use

To determine rates of cross-sensitivity of rash among commonly used antiepileptic drugs (AEDs) in patients with epilepsy.

The incidence of AED-related rash was determined in 1875 outpatients (> or =12 years), taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), levetiracetam (LEV), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproic acid (VPA), or zonisamide (ZNS). We compared rates of rash for each AED in patients with vs those without a rash to 1) another specific AED; 2) any other AED; 3) any two other AEDs; and 4) any non-epilepsy medication.

A total of 14.3% (269/1,875) of patients had a rash attributed to at least one AED; 2.8% had a rash to two or more AEDs. Of patients who had a rash to CBZ and were also prescribed PHT (n = 59), 57.6% had a rash to PHT (abbreviated as CBZ --> PHT: 57.6%); of patients who had a rash to PHT and were also prescribed CBZ (n = 81), rate of rash was 42% (i.e., PHT --> CBZ: 42%). Other results: CBZ --> LTG: 20% (n = 50); LTG --> CBZ: 26.3% (n = 38); CBZ --> OXC: 33% (n = 15); OXC --> CBZ: 71.4% (n = 7); CBZ --> PB: 26.7% (n = 30); PB --> CBZ: 66.7% (n = 12); LTG --> PHT: 38.9% (n = 36); PHT --> LTG: 18.9% (n = 74); PB --> PHT: 53.3% (n = 15); PHT --> PB: 19.5% (n = 41); OXC --> LTG: 37.5% (n = 8); LTG --> OXC: 20% (n = 15). There was evidence of specific cross-sensitivity between CBZ and PHT, and between CBZ and PB.

Cross-sensitivity rates between certain antiepileptic drugs (AEDs) are high, especially when involving carbamazepine and phenytoin. Specific cross-sensitivity rates provided here may be useful for AED selection and counseling in individual patients.