New Formulary Additions:Lacosamide (VIMPAT) Oral and IV for the

Treatment of Partial Onset Seizures

Jason Yung, PharmD StudentLeslie Dan Faculty of Pharmacy

University of Toronto

Case: Should John Smith get Lacosamide at NYGH?

• JS = 40M brought into ED, 5yr Hx of partial onset seizures

• JS tried and failed monotherapy with lamotrigine and carbamazepine

• He has been taking carbamazepine and valproic acid (AEDs) for 3 yrs, but has had recurrent seizures for the past 1 month

• Neurologist consulted ordered lacosamide 50mg IV BID

Learning Objectives• Describe seizure etiology and goals of therapy

for patients experiencing seizures• List therapeutic alternatives for seizures• Provide benefits and drawbacks of using

lacosamide (nursing considerations)• Appropriately administer and monitor use of

lacosamide for treatment of partial-onset seizures at NYGH

Epilepsy and Goals of Therapy• Epilepsy: predisposition to

unprovoked seizures (uncontrolled brain electrical activity)

• Risk factors: intracranial infection, head trauma, stroke, family Hx of seizures, etc.

• Goals: control seizures, manage side effects, restore quality of life

How do we control seizures?NON-PHARMACOLOGICAL

Cocaine and Amphetamines

Sleep deprivation Alcohol indulgencesAVOID… AVOID… AVOID…

OR, if seizures are resistant to multiple AEDs Epilepsy surgery

How do we control seizures?PHARMACOLOGICAL

• Start: single AED, fraction of initial target dose– ADR = dose; Recurrent seizures = dose

• Uncontrolled seizures by max tolerated dose of single AED…– Add on a 2nd AED– Gradually withdraw 1st AED when maintenance of

2nd AED is achieved• If monotherapy with 2-3 drugs fails to control

seizures, consider polytherapy with AEDs

How do we control seizures?PHARMACOLOGICAL

• Adults who experience seizures may require 2-3 agents for adequate control

• Some drugs currently available on formulary for management of partial onset seizures:– Carbamazepine PO (1st line)– Lamotrigine PO (1st line; better tolerated vs. carbam.)– Topiramate PO– Oxcarbezepine PO– Levetiracetam PO– Phenytoin PO/IV– Valproic Acid PO/IV– Lacosamide PO/IV

Dosage forms carried in NYGH:10mg/mL (20mL), 50mg, 100mg

Available in the ED Resus Omnicell!

Lacosamide• Mechanism: prevents repetitive neuronal firing• NOT a 1st line medication for epilepsy• Used as ADJUNCT therapy for uncontrolled

partial onset seizures in adults on ≥ 2 AEDs

Criteria for Use: “TWO NAP”

After a seizure, pts may want “TO NAP”:• TWO: on 2+ suitable AEDs

that are not effective or tolerated

• N: Neurologist prescribed• A: Adult patient (≥ 18yrs)• P: Partial onset seizure

diagnosis

Lacosamide Dosing• Initial Dose: 50 mg BID (no loading dose)– May increase weekly by 50mg BID based on pt

response and tolerability• Maintenance Dose: 100 - 200mg BID– Max Dose: 400 mg/d

• PO given with or without food• Withdraw slowly (min. 1 wk) to reduce

potential for increased seizure frequency

IV Lacosamide Dosing

• Lacosamide IV is restricted to patients unable to take lacosamide PO

• Oral to IV switch: dose and frequency conversion is 1:1– i.e. 50mg BID PO = 50mg BID IV

• IV route to be used for a max of 5 days (switch to PO as soon as practical)

Clinical MonitoringCARDIAC RENAL HEPATIC

GI CNS

CARDIAC Monitoring

• Dose-related PR interval prolongation– May predispose pts to AFib and Atrial

flutter – CAUTION: carbamazepine and lamotrigine

may further prolong PR interval• Obtain ECG for pts with known

conduction problems or Hx of severe cardiac disease

RENAL Monitoring

• 95% is renally eliminated– Renal impairment = drug accumulation = toxicity

• Monitor SCr and CrCl• CrCl ≤ 30mL/min or ESRD = Max 300mg/day – CrCl > 30mL/min = Max 400mg/day

HEPATIC Monitoring

• Monitor LFTs (ALT, AST)– ALT ≥ 3X upper limit of normal in 0.7% lacosamide

pts (vs. 0% placebo pts)• Mild-to-Moderate hepatic impairment = Max

dose 300mg/day– NOT recommended in pts with severe hepatic

impairment

• Dizziness (30%)• Headache (14%)• Nausea (11%)• Blurred vision (9%)• Nasopharyngitis (8%)• Ataxia (7%)• Fatigue (7%)

Note: events are dose-related (mainly

400mg/day)

GI + CNS Monitoring

ContraindicationsWhen to NOT use Lacosamide:• Hypersensitivity to

lacosamide or excipients– Triad: rash, fever, organs

involved– SJS

• Allergy to soy or peanuts– Cross-reaction to soy lecithin

found in tablet film coating• Hx of 2nd or 3rd degree AV

block

BENEFITS of using Lacosamide:

No drug interactions with other AEDs

TDM not required (cf. carbamazepine, phenytoin, valproic acid) which helps…• Nursing staff: fewer blood samples

drawn• Lab services: fewer blood samples

analyzed• Hospital budgeting: cost savings

from reduced TDM

DISADVANTAGES to using Lacosamide:

Nursing considerations: ECG’s are performed…– Prior to therapy initiation– After ~ 3 days (steady state)– Changes to dose

Case: Should John Smith get Lacosamide at NYGH?

• JS = 40M brought into ED, 5yr Hx of partial onset seizures

• JS tried and failed monotherapy with lamotrigine and carbamazepine

• He has been taking carbamazepine and valproic acid (AEDs) for 3 yrs, but has had recurrent seizures for the past 1 month

• Neurologist consulted ordered lacosamide 50mg IV BID

Yes! Recall “TWO NAP” Criteria…• “TWO” AEDs (carbamazepine and

lamotrigine) & seizures are not controlled

• Neurologist ordered• Adult (40yr old patient)• Partial onset seizure diagnosis

Case: Should John Smith get Lacosamide?

How do you administer Lacosamide 50mg IV BID?

• 50mg = Draw 5mL from 10mg/mL stock (20mL stock)

• Mix 5mL stock with 100mL NS or D5W• Administer IV infusion over 30-60 mins• Administer 2nd dose after ~ 12hrs• 1 stock of 10mg/mL (20mL) will provide 4 doses of

50mg (2 days supply)

** Info found in IV monograph on NYGH Intranet **

Summary for Practice:

• Criteria for use is “TWO NAP”• PO to IV dose and freq. conversion is 1:1• If PO lacosamide not feasible IV lacosamide x max 5

days• ECG performed prior to use to r/o abnormal cardiac

conduction• Monitoring head-to-toe:– CNS: dizziness, headache, fatigue– Cardiac: PR interval prolongation– Hepatic: LFTs (ALT)– Renal: Sr, CrCl (adjust dose when ≤ 30mL/min)– GI: nausea

- Thank You -

ED StaffSpecial Thanks: Nicole Crichton, RPh

Questions?