lacosamide and Diplopia

Analysis of overall tolerability and neurological adverse effects (AEs) of eslicarbazepine acetate (ESL), lacosamide (LCM) and oxcarbazepine (OXC) from double-blind, placebo-controlled trials. Indirect comparisons of patients withdrawing because of AEs, and the incidence of some vestibulocerebellar AEs between these three antiepileptic dugs (AEDs).. We searched MEDLINE for all randomized, double-blind, placebo-controlled trials investigating therapeutic effects of fixed oral doses of ESL, LCM and OXC in patients with drug resistant epilepsy. Withdrawal rate due to AEs, percentages of patients with serious AEs, and the proportion of patients experiencing any neurological AE, nausea and vomiting were assessed for their association with the experimental drug. Analyses were performed between recommended daily doses of each AED according to the approved summary of product characteristics (SPC). Risk differences were used to evaluate the association of any AE [99% confidence intervals (CIs)] or study withdrawals because of AEs (95% CIs) with the experimental drug. Indirect comparisons between withdrawal rate and AEs dizziness, coordination abnormal/ataxia and diplopia were estimated according to network meta-analysis (Net-MA).. Eight randomized, placebo-controlled, double-blind trials (4 with ESL, 3 with LCM, and 1 with OXC) were included in our analysis. At high doses (OXC 1200mg, ESL 1200mg and LCM 400mg) there was an increased risk of AE-related study withdrawals compared to placebo for all drugs. Several AEs were associated with the experimental drug. Both number and frequency of AEs were dose-related. At high recommended doses, patients treated with OXC withdrew from the experimental treatment significantly more frequently than patients treated with ESL and LCM. Furthermore, the AEs coordination abnormal/ataxia and diplopia were significantly more frequently observed in patients treated with OXC compared to patients treated with LCM and ESL.. The overall tolerability of AEDs and the incidence of several neurological AEs were clearly dose-dependent. Indirect comparisons between these AEDs, taking into account dose-effect, showed that OXC may be associated with more frequent neurological AEs than LCM and ESL.

Topics: Acetamides; Anticonvulsants; Ataxia; Carbamazepine; Dibenzazepines; Diplopia; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Lacosamide; Nervous System Diseases; Oxcarbazepine; Randomized Controlled Trials as Topic; Risk Assessment; Sodium Channel Blockers; Treatment Outcome

Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial-onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200-800 mg/day) infused over 10, 15, and 30 min as short-term replacement for oral lacosamide in patients with partial-onset seizures.. This multicenter, open-label, inpatient trial enrolled 160 patients from ongoing open-label, long-term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2-5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations.. A total of 160 patients received lacosamide 200-800 mg/day, i.v., for 2-5 days, of which 69% received 400-800 mg/day doses. The most common AEs (reported by or=400 mg/day). Injection-site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts.. This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short-term (2-5 days) replacement for patients temporarily unable to take oral lacosamide.

Topics: Acetamides; Administration, Oral; Adult; Aged; Cohort Studies; Diplopia; Drug Administration Schedule; Epilepsies, Partial; Female; Humans; Infusions, Intravenous; Internationality; Lacosamide; Male; Middle Aged; Seizures; Young Adult

A 73-year-old woman presented with transient episodes of dysarthria and horizontal diplopia. She had stereotactic radiosurgery 18 years prior for a retroclival meningioma. Neurologic examination was notable for right-sided tongue deviation, tongue fasciculations, and intermittent impaired abduction of the right eye. MRI ruled out recurrence or progression of the retroclival meningioma. EEG failed to reveal electrographic seizures. EMG showed spontaneous depolarizations in bursts that sounded like "marching soldiers" in the right hemitongue, consistent with myokymia. Focal myokymia is an unusual EMG finding that is usually seen in demyelinating disorders, after radiation, or in neoplastic/inflammatory conditions. The clinical presentation and EMG findings were most consistent with delayed radiation-induced myokymia. Similar cases of transient dysarthria and tongue myokymia from radiation have been infrequently reported in the literature; however, this case uniquely exhibited additional episodes of transient horizontal diplopia, which was possibly from ocular myokymia or neuromyotonia. Although there are limited data, sodium channel inhibitors (e.g., carbamazepine, oxcarbazepine, and lacosamide) have shown some success to provide symptomatic relief, most likely secondary to their ability to inhibit underlying peripheral nerve hyperexcitability. Our patient was started on lacosamide 50 mg twice a day with a notable decrease in symptom frequency. This case illustrates the importance of detailed clinical and electrodiagnostic studies in making the diagnosis of delayed radiation-induced myokymia with episodic dysarthria and provides guidance on potential therapeutics.

Topics: Aged; Clinical Reasoning; Diplopia; Dysarthria; Female; Humans; Lacosamide; Meningeal Neoplasms; Meningioma; Myokymia