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A 13-year-old girl presented with rash and fever while vacationing in the United States. Five weeks earlier, in her home country, the United Kingdom, she began perampanel (Fycompa; Eisai, Tokyo, Japan) for treatment of drug-resistant epilepsy. Her history includes prenatal exposure to IV drugs and postnatal development of mild left hemiparesis with associated right periventricular leukomalacia. At age 9 months, she began having left-sided focal seizures. She developed an epileptic encephalopathy manifested by cognitive regression associated with continuous spike wave in slow wave sleep more prominent over the right hemisphere. Medication history included phenobarbital, rufinamide, sultiame, clobazam, lacosamide, and levetiracetam, all discontinued because of poor seizure control or toxicity. Her epilepsy stabilized on lamotrigine and valproic acid over 2 years with good control of her generalized tonic and tonic-clonic seizures. She still experienced daily breakthrough negative myoclonic seizures, for which perampanel was started, initially at 2 mg QHS, increasing to 4 mg QHS after 4 weeks.