Carbamazepine/lacosamide/lamotrigine interaction

Abstract

Aggravation of myoclonic seizures and absences seizures: 3 case reports In a case series, three woman aged an approximately 28–47 years were described, who developed myoclonic seizures or had an aggravation of juvenile myoclonic seizures or juvenile absences seizures during treatment with carbamazepine, lacosamide or lamotrigine. Out of 3 women, two women exhibited drug interaction following concomitant administration of carbamazepine, lacosamide or lamotrigine [routes not stated, not all dosages and durations of treatments to reactions onsets stated]. Case 1: A 47-year-old woman experienced an aggravation of juvenile myoclonic seizures following concomitant treatment with carbamazepine and lacosamide for generalised tonic-clonic seizures. The woman presented to the clinic due to increased number of seizures. She had myoclonic jerks since 13 years of her age and was successfully treated with phenobarbital for five years. But, phenobarbital was changed to carbamazepine. While receiving carbamazepine, she had absence and myoclonic seizures once every week and generalised tonic-clonic seizures every few years. Thus, lacosamide 350 mg/day (150mg in the morning and 200mg at night) was added to carbamazepine 1000 mg/day treatment three years before. However, she experienced increase in myoclonic seizures every day and up to three generalised tonic-clonic seizures every month while receiving carbamazepine and lacosamide. An electroencephalography demonstrated background slowing with excess beta waves and generalised polyspike and slow wave discharges. Thus, she received alprazolam and subsequently she was diagnosed with juvenile myoclonic epilepsy. It was considered that the aggravation of myoclonic seizures was secondary to drug interaction cause by synergetic effect following concomitant administration of carbamazepine and lacosamide. Therefore, lacosamide was stopped gradually and valproate was started. At the next follow-up visit, she had no absences, myoclonus or generalised tonic-clonic seizures while receiving carbamazepine and valproate. A repeated electroencephalography showed generalised polyspike and slow wave discharges with normal background. Subsequently, carbamazepine was slowly stopped and an electroencephalography was performed seven months later that showed normal background with no epileptiform discharges. She remained seizure free. Case 2: A 34-year-old woman experienced an aggravation of juvenile myoclonic seizures following concomitant treatment with lacosamide and lamotrigine for juvenile myoclonic epilepsy. She also received levetiracetam and lamotrigine during pregnancy: The woman had refractory juvenile myoclonic epilepsy that started at the age of 14 years. She was treated with valproate, lamotrigine, levetiracetam, topiramate and phenobarbital. But, she had no seizure control. During treatment with valproate, topiramate and lamotrigine, she experienced generalised tonic-clonic seizures bimonthly and myoclonic seizures every week. Later, she underwent planned pregnancy. Thus, valproate and topiramate were stopped and levetiracetam 2000 mg/day was initiated without significant change in seizure control. She received levetiracetam and lamotrigine during the pregnancy and subsequently delivered a healthy baby via caesarean section. Thereafter, lacosamide 100mg twice a day was added to her treatment with lamotrigine 150 mg/day and levetiracetam. Two weeks after initiation of lacosamide, she had increase in the frequency of myoclonic seizures. Thus, an electroencephalography was performed that showed multiple generalized polyspike and slow wave discharges enhanced by sleep. It was considered that the aggravation of myoclonic seizures was secondary to drug interaction cause by synergetic effect following concomitant administration of lacosamide and lamotrigine. Hence, lacosamide was stopped after two months and the frequency of myoclonus decreased. At the follow-up visit, an electroencephalography showed no epileptiform discharges. Case 3: An approximately 28-year-old woman developed myoclonic seizures and had an aggravation of juvenile absences seizures during treatment with lacosamide for generalised tonic-clonic seizures. The woman developed absence seizures and occasional generalised tonic-clonic seizures at the age of 13 years and diagnosed with juvenile absence epilepsy. Thus, she received carbamazepine with continued seizures. Hence, topiramate was given that led to improvement in the generalised tonic-clonic seizures. However, she had cognitive side effects secondary to topiramate. Subsequently, she started receiving valproate at the age of 21 years that led to complete seizure remission. Seven years later, she was planning pregnancy. Thus, valproate was switched to lamotrigine and levetiracetam. But, she had generalised tonic-clonic seizures every month and experienced intolerable unspecified side effects. Thus, lamotrigine and levetiracetam were discontinued and lacosamide 50 mg/day was initiated that increased by 50mg each week up to 100mg twice a day for one year. While receiving lacosamide, she had relapse of daily absences and a new onset of myoclonic seizures every week. An electroencephalography multiple generalized polyspike and slow wave discharges enhanced by photo-stimulation and hyperventilation. It was considered that the new onset of myoclonic seizures and an aggravation of absences seizures were secondary to lacosamide. Thus, lacosamide was stopped and lamotrigine and levetiracetamwere resumed that restored her to the previous clinical condition. Her repeated electroencephalography showed resolution of absences, myoclonic seizures and epileptiform discharges with occurrence of generalised tonic-clonic seizures every month.