In the October WMSHP Newsletter, Julie Pardy, a PGY-1 Pharmacy Resident at Spectrum Health, reviews the use of lacosamise for partial onset seizures.

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Lacosamide (Vimpat^®) for Partial Onset Seizures

Julie Pardy, PharmD, PGY-1 Pharmacy Resident

Despite extensive research and multiple treatment options, the ideal anti-epileptic is yet to be found. Patients that suffer from epilepsy often find themselves taking multiple medications, experiencing adverse reactions, requiring serum drug monitoring, and still experiencing seizures.

In October of 2008, Lacosamide (Vimpat^®) was approved as an adjunctive treatment for partial onset seizures in patients 17 years of age and older. Lacosamide is available as an oral tablet (50 mg, 100 mg, 150 mg, and 200 mg), oral solution (10 mg/mL), and solution for injection (10 mg/mL). Lacosamide has a novel mechanism of action. Lacosamide selectively enhances slow inactivation of sodium channels, this causes decreased neuronal hyperactivity while preserving physiological activity. Additionally, lacosamide has shown evidence of activity at the collapsing response mediator protein 2 (CRMP-2). CRMP-2 has multiple actions including neuronal differentiation and regulation of gene expression. However, the clinical significance of CRMP-2 in seizure control is unknown. There is some evidence in animal models that CRMP-2 inhibition may prevent neuronal development and this is why in Helen DeVos Children’s Hospital (HDVCH) we are not recommending lacosamide for infants less than 1 year old.

Many aspects of lacosamide’s pharmacokinetic profile are favorable. It has 100% oral bioavailability, it has rapid absorption that is not affected by food, and it has a long half life allowing for twice daily dosing. Its 100% bioavailability allows for equivalent daily doses when switching from IV to oral formulations. Additionally, it has low protein binding and has predominately renal elimination as unchanged drug (>40%). Lacosamide has minimal CYP 450 interactions.

Lacosamide is generally well tolerated by patients. The most common adverse effects with the oral formulations include dizziness, headache, nausea and diplopia. All of these adverse effects were dose related except for headache, which was more predominant during dosage titration. Adverse effects associated with the IV formulation include those of the oral formulation as well as injection site pain. The most predominant adverse effect and most likely cause for discontinuation is dizziness. Of note, lacosamide may prolong the PR interval, so patients at risk for arrhythmias should have cardiac monitoring performed prior to therapy.

Lacosamide is initially dosed in adults at 50 mg twice daily with dose titrations at weekly intervals by 100 mg/day. The maintenance dose is usually between 200 to 400 mg/day for most patients. In a human abuse study, lacosamide produced euphoria in 15% of patients when dosed at 800 mg leading to its schedule V status. The incidence of euphoria was minimal (<1%) in clinical trials at therapeutic doses.

As stated previously, lacosamide is only indicated as adjunctive therapy of partial onset seizures in patients 17 years of age and older. However, ongoing research suggests that lacosamide may have a role in other types of seizures as well as treatment refractory status epilepticus. Currently there is a lack of data and dosing recommendations for pediatric patients, although there are two ongoing multicenter dose-ranging pharmacokinetic trials for this population. The dosing recommended and approved for use in HDVCH is provided in the table below and is based on the on-going studies.

Lacosamide is being investigated as a treatment option for diabetic neuropathic pain, fibromyalgia, and migraine prophylaxis. With its novel mechanism of action and favorable pharmacokinetic and safety profile, there is no doubt that we will be seeing more of this drug in the future.

 

Pediatric Lacosamide (Vimpat^®) Dosing

Loading Dosing (oral or IV):	2-4 mg/kg/dose (max dose of 200 mg)
Maintenance Dosing (oral or IV):	4-6 mg/kg BID (max 400 mg/day)
Note: Pharmacokinetic and efficacy studies are not available in children. Dosing is provided per clinicaltrials.gov on-going investigational studies.

 

References

1. Halford et al. Clinical Perspectives on Lacosamide. Epilepsy Currents. 2009; 9(1): 1-9.
2. Kelemen and Halasz. Lacosamide for the Prevention of Partial Onset Seizures in Epileptic Adults. Neuropsychiatric Disease and Treatment. 2010; 6: 465-471.
3. Vimpat [package insert]. Smyrna, GA: UCB, Inc; 2011.
4. Chung. New Treatment Option for Partial-Onset Seizures: Efficacy and Safety of Lacosamide. Ther Adv Neurol Disord. 2010: 3(2): 77-83.
5. Kellinghaus. Lacosamide as Treatment for Partial Epilepsy: Mechanisms of Action, Pharmacology, Effects and Safety. Therapeutics and Clinical Risk Management. 2009; 5: 757-766.
6. Abou-Kalil. Lacosamide: What can be expeted from the next new antiepileptic drug? Epilepsy Currents. 2009; 9(5): 133-134.
7. A Multicenter, Open-Label Study to Investigate the Safety and Pharmacokinetics of Lacosamide in Children with Partial Seizures. NCT00938431. Last updated on July 25, 2011.
8. The Safety of Intravenous Lacosamide. NCT00832884. Last updated on Mar 5, 2010.
9. An Open-label Extension Study to Determine Long-Term Safety, NCT00938912. Last updated 25, 2011.