175481-36-4

Hazard Information

Questions And Answer

• Description

  Lacosamide (LCM), (SPM 927, (R)-2-acetamido-N-benzyl-3-methoxypropionamide, previously referred to as harkoseride or ADD 234037) is a member of a series of functionalized amino acids that were specifically synthesized as anticonvulsant or antiepileptic drug. It reduces the spread of seizure activity in the brain. Lacosamide appears to have a dual mode of action: selective enhancement of sodium channel inactivation and modulation of collapsin response mediator protein-2.  Compared to novel antiepileptic drugs, lacosamide has broader and higher efficacy, better tolerability, and improved pharmacokinetic properties. Lacosamide is in phase III clinical development for adjunctive treatment of patients with uncontrolled partial-onset seizures, and for monotherapy of patients with painful diabetic neuropathy. It is absorbed rapidly and completely after oral administration. Lacosamide has an elimination half-life of approximately 13 hours and a low potential for drug interactions. Additionally, lacosamide exhibits linear, dose-proportional pharmacokinetics with low intra- and interpatient variability.
  Lacosamide (licensed in 2008) is a third- generation AED known with the proprietary brand name of Vimpat® (UCB Pharma, Slough) in the UK and USA. ;

• Generic formulation

  MHRA/ CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (incl. generic products):
  • It is usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product unless there are specific concerns, such as patient anxiety and risk of confusion/ dosing error.
  ;

• Indications

  Epilepsy: Adjunctive treatment of focal seizures with or without secondary generalization. ;

• Dose titration

  • Epilepsy— adjunctive therapy: 50 mg bd for 7 days, then increased by 50 mg bd every 7 days; usual maintenance 100 mg bd (max. 200 mg bd).
  • Epilepsy— adjunctive therapy (loading dose regimen when it is necessary to rapidly attain therapeutic plasma concentrations, under close medical supervision): 200 mg bd for 1 day, followed by maintenance dose of 100 mg bd after 1 day, then increased if needed by 50 mg bd every 7 days (max. 200 mg bd).
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• Uses

  Lacosamide is an anticonvulsant and analgesic compound used for the treatment of partial-onset seizures and neuropathic pain. It can also used for the treatment of status epilepticus. Its analgesic effect is mediated by its inhibitory effect on sodium channels, which leads to neural membrane depolarization. Its interaction with the collapsin-response mediator protein 2 (CRMP-2 alias DRP-2) may also facilitate the above process, although the detailed mechanism remains to be elucidated.  ;

• Side effects

  Lacosamide was generally well tolerated in adult patients with partial-onset seizures.[11] The side-effects most commonly leading to discontinuation were dizziness, ataxia, diplopia (double vision), nystagmus, nausea, vertigo and drowsiness. These adverse reactions were observed in at least 10% of patients.[9] Less common side-effects include tremors, blurred vision, vomiting and headache.

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• Cautions

  • Patients with conduction problems (contraindicated in patients with second- or third- degree A– V block).
  • Patients with severe cardiac disease.
  • Patients at risk of PR- interval prolongation.
  • Elderly patients.
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• Interactions

  With AEDs
  Concomitant treatment with other AEDs known to be enzyme inducers (such as carbamazepine, phenobarbital, phenytoin) decreases the overall systemic exposure of lacosamide by 25%.
  
  With other drugs
  Nil.
  
  With alcohol/food
  • Although no pharmacokinetic data on the interaction of lacosamide with alcohol are available, a pharmacodynamic effect cannot be excluded.
  • There are no specific foods that must be excluded from diet when taking lamotrigine.
  ;

• Special populations

  Hepatic impairment
  • Titrate with caution in mild- to- moderate impairment if co- existing renal impairment.
  • Caution in severe impairment.
  
  Renal impairment
  • Loading dose regimen can be considered in mild- to- moderate impairment (titrate above 200 mg with caution).
  • Titrate with caution in severe impairment (max. 250 mg daily).
  
  Pregnancy
  • There are no adequate data from the use of lacosamide in pregnant women and the potential risk for humans is unknown.
  • Lacosamide should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus). If a woman decides to become pregnant, the use of lacosamide should be carefully re- evaluated. In case of treatment with lacosamide, the dose should be monitored carefully during pregnancy and after birth, and adjustments made on a clinical basis.
  • Lacosamide has been found to be present in milk in animal studies and it is recommended that it should be avoided during breastfeeding
  ;

• Behavioural and cognitive effects in patients with epilepsy

  For this third- generation agent, clinical experience is still limited and little is known about its positive and negative psychotropic properties and their implications for the management of behavioural symptoms in patients with epilepsy. There are initial reports of depression, irritability and agitation, and psychotic symptoms. Reports of cognitive effects (mainly affecting attention and memory) are rare and usually not severe. ;

• Psychiatric use

  Lacosamide has no indications for the treatment of psychiatric disorders. There is insufficient experience with lacosamide to draw any conclusion regarding its psychotropic profile. ;

• References

  [1] B. K. Beyreuther, J. Freitag, C. Heers, N. Krebsfänger, U. Scharfenecker, T. Stöhr (2007) Lacosamide: a review of preclinical properties, CNS Drug Reviews, 13, 21-42
  [2] Beyreuther, Bettina K., et al. "Lacosamide: A Review of Preclinical Properties." Cns Drug Reviews 13.1(2007):21.
  [3]Chung, S, et al. "Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial." Epilepsia 51.6(2010):958–967.
  [4]Kellinghaus, C, et al. "Intravenous lacosamide for treatment of status epilepticus." Acta Neurologica Scandinavica 123.2(2011):137–141. ;

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