Lacosamide Injection

Brand names Vimpat

Medication error May be confused with zonisamide potential

Contraindications Contraindications: None and warnings Warnings: Use cautiously in patients with known cardiac conduction problems (e.g., second-degree atrioventricular block), who are taking drugs known to prolong the PR interval, or in those with severe cardiac disease. May cause syncope. Do not discontinue abruptly, but gradually withdraw over a minimum of 1 week to minimize the potential of increased seizure frequency.(1) Multiorgan hypersensitivity reactions have been reported.(1) (See the Comments section.)

Infusion-related One report of bradycardia has been noted during a 15-minute infusion in a patient con- cautions currently receiving a beta-blocker. Heart rate rapidly returned to normal upon discontinu- ation of lacosamide.(1) Infusion site reactions including injection site pain or discomfort, irritation, and erythema may occur.(1)

Dosage IV lacosamide is FDA-labeled as adjunctive therapy for partial-onset seizures in patients with epilepsy who are 17 years and older when oral administration is temporarily not feasible.(1) IV and oral administration is equivalent in dose and frequency.(1) When switch- ing from oral therapy, the initial total daily IV dosage should be equivalent to the total daily dosage and frequency of oral lacosamide and should be infused intravenously over a period of 30–60 minutes.(1) Adults: Although it is not FDA-approved for status epilepticus (SE), it has been successfully used in refractory SE in adults.(8,9) A 2013 review paper found 19 publications, including 10 case reports and 9 case series, reporting IV lacosamide for the treatment of SE.(24) Most adults received 200–400 mg as a loading dose followed by 200 mg q 12 hr. There is experience with IV BID infusion for up to 5 days.(1) Pediatrics: The safety and efficacy of lacosamide in adults, and the occasional shortage of other parenteral anticonvulsants, has led to the use of lacosamide in refractory SE. Although it has been given orally in pediatric patients (as young as 1 year of age) for adjunctive therapy for refractory partial-onset seizures (including Lennox-Gastaut syn- drome [LGS])(10-13) and orally for refractory SE,(14) there is insufficient information regard- ing dosing, efficacy, and safety of the IV product in pediatric patients with refractory SE. Oral dose in adjunctive therapy for partial onset seizures: Normal mainte- nance doses range from 6–12 mg/kg/day divided BID. Because dosing with oral and IV therapy are equivalent, the information below may assist practitioners who use IV lacosamide as replacement for those patients on lacosamide who temporarily can not take oral therapy. Refractory status epilepticus: At this time lacosamide is considered a second- or third-like agents in the management of refractory SE.(26-28) Eleven children (mean age: 9.4 years) with refractory convulsive or nonconvulsive SE received IV lacosamide. The mean initial loading dose was 8.6 mg/kg (range: 6.7–9.9) followed by 12.9 mg/kg/day (range: 9.1–13.9). Lacosamide was effective in stopping RSE in 45% of patients, with seizures terminating within 12 hours in three children. No serious adverse events attributable to lacosamide.(23) The case series (n = 3) described the successful use of lacosamide in patients (12–17 years) with refractory tonic SE. After three or more standard anticonvulsants were tried over the course of 8–29 hours, an IV loading dose of lacosamide (2–2.5 mg/ kg) was given. Two patients responded to a single dose, and 1 patient required 2 doses of lacosamide.(25) An 8-year-old boy with refractory SE, which had persisted for 10 weeks, received oral lacosamide (25 mg BID). The number of seizures decreased within 3 days and stopped within 5 days.(14)  540 Lacosamide Injection

Dosage (cont.) A 17-year-old was given IV lacosamide for either seizure clusters or refractory SE.(5) Adults who had SE received an initial loading dose of 200–400 mg followed by a median of 200 mg (200–400 mg).(5)

Dosage adjustment If CrCl is <30 mL/min in adults, the dose should not exceed 300 mg/day.(1) Because in organ dysfunction lacosamide is removed by a 4-hour hemodialysis session, a supplemental dose (up to 50%) should be given after dialysis.(1) The maximum dose in adults with mild-to-moderate hepatic impairment is 300 mg/day.(1) Use is not recommended in those with severe hepatic impairment.(1)

Maximum dosage Not established. 20 mg/kg/day divided BID in pediatrics.(12) 600 mg/day(15) orally and 400 mg(5) IV in adults. In a clinical trial, a daily dose of 600 mg was not more effective than a daily dose of 400 mg and was associated with a higher rate of adverse effects.(16)

Additives None

Suitable diluents NS, D5W, LR(1)

Maximum 10 mg/mL (commercially available)(1) concentration

Preparation and Parenteral products should be visually inspected for particulate matter and discoloration delivery before use. Refer to appropriate references for more information on compatibility with other drugs and solutions; compatibility following Y-site delivery, and suggested storage and extended stability.(3) Diluted solution may be stored at room temperature for 4 hours, but any unused por- tion should then be discarded as the product does not contain a preservative.(1) When mixed in suitable diluent and placed in glass or PVC bag, it is stable for 24 hours at room temperature (15°C to 30°C).(1) If particulate matter or discoloration noted, the product should not be used.(1)

IV push Not recommended

Intermittent infusion Has been given over 15 minutes, but infusion over 30–60 minutes is preferred.(1) Some have given at rates of 60 mg/min(5) up to 80 mg/min in adults.(7)

Continuous infusion No reports of administration by this method

Other routes of None administration

Comments Rare adverse effects Anticonvulsant hypersensitivity syndrome/DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome: This acute, life-threatening, idiosyncratic reaction that has been reported in patients receiving lacosamide.(1,22) Symptoms generally develop within 1–12 weeks following initiation and include a classic triad of fever, rash, and lymphadenopathy. Peripheral blood leucocytosis and eosinophilia and internal organ involvement may also occur. Immediate discontinu- ation of the suspected anticonvulsant is essential for good outcome. Patients who experience this adverse effect should not be given an anticonvulsant with an aromatic structure (phenytoin, phenobarbital, carbamazepine, primidone, and lamotrigine) as cross-reactivity has been noted.(19-21)  541