lacosamide

Lacosamide is an anticonvulsant medication used to treat epileptic conditions including partial-onset seizures and primary generalized tonic-clonic seizures. Seizures are caused due to abnormal electrical activity in hyperexcitable nerve cells (neurons) in the brain. Partial (focal) onset seizure is a type of seizure in which abnormal electrical activity is confined to a limited area of the brain. Primary generalized tonic-clonic seizures arise in both sides of the brain, spread rapidly, and cause violent muscle contractions and loss of consciousness.

Lacosamide is an antiepileptic drug that reduces the potential for abnormal electrical activity that cause seizures. Lacosamide enhances the slow inactivation of voltage-gated sodium channels, stabilizing the hyperexcitable neuronal membranes and inhibiting repetitive firing of neurons. Lacosamide affects only neurons that are hyperactive, typically at the focal point of epileptic seizures. Lacosamide selectively enhances the slow inactivation of sodium channel and has no effects on fast inactivation of sodium channels.

Lacosamide also has neuroprotective effects and may inhibit repetitive seizures by binding to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein in the nervous system that is believed to be implicated in both epilepsy and neuropathic pain. Clinical trials have been conducted with lacosamide in patients with diabetic neuropathy, however, lacosamide is not approved for this use. Lacosamide is available as oral tablets, capsules and solution and as an intravenous injection solution. The uses of lacosamide include:

FDA-approved:

• Monotherapy or adjunctive therapy for partial-onset seizures in adults and children of age one month or older
• Adjunctive therapy for primary generalized tonic-clonic seizures in adults and children 4 years and older

Off-label:

• Status epilepticus, a prolonged state of seizure that is a medical emergency

• Antiepileptic drugs including lacosamide can increase the risk of suicidal thoughts and behavior in patients. Caution patients, their family and caregivers about this risk, and advise them to be alert for and report any emergence or worsening of depression or suicidal thoughts, or unusual changes in mood and behavior.
• Lacosamide can cause dizziness and impairment of balance, coordination and speech (ataxia), most commonly during titration of doses. Caution patients to avoid engaging in hazardous activities until the drug’s effects can be determined.
• Lacosamide can cause cardiac rhythm and conduction abnormalities including bradycardia, atrioventricular (AV) block or ventricular tachyarrhythmia that can result in flatline (asystole), cardiac arrest and death.
  • The risk of heart conduction abnormalities is higher in patients who have preexisting irregular heart rhythms, severe cardiovascular diseases, or in those taking medications that affect cardiac conduction or prolong PR interval.
  • In patients at risk for heart conduction abnormalities, obtain ECG before starting lacosamide and closely monitor if it is administered intravenously.
  • Use lacosamide with caution in patients with cardiovascular conditions such as AV block, sick sinus syndrome without pacemaker, Brugada syndrome, myocardial ischemia, heart failure or structural heart disease.
  • Use lacosamide with caution in patients who are concurrently taking medications that affect cardiac conduction such as sodium channel blockers, beta blockers, calcium channel blockers and potassium channel blockers.
  • Lacosamide may also cause atrial flutter and fibrillation and the risk is higher in patients with diabetic neuropathy and/or cardiovascular disease.
• There have been reports of loss of consciousness (syncope), many of which were associated with orthostatic changes in blood pressure, bradycardia, or atrial flutter/fibrillation and associated tachycardia, primarily in patients with diabetic neuropathy, high risk factors for cardiovascular disease, or patients taking drugs that slow AV conduction.
• Lacosamide can cause a drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multi-organ hypersensitivity that can be life-threatening or fatal. If a patient develops fever, rash, facial and/or lymph node swelling, in association with inflammation in other organs including hepatitis, nephritis, myocarditis, myositis, or blood abnormalities, assess the patient for DRESS and discontinue lacosamide immediately if there are no alternate reasons for the symptoms.
• The oral formulation of lacosamide contains aspartame, a source of phenylalanine. Prescribe it with caution after considering the cumulative phenylalanine intake in patients with phenylketonuria, a disorder with inability to metabolize phenylalanine.

Serious side effects of lacosamide include:

• Suicidal ideation and behavior
• Dizziness
• Impaired balance, coordination and speech (ataxia)
• Cardiac rhythm and conduction abnormalities including:
  • PR interval prolongation
  • Atrioventricular block
  • Rapid and irregular contraction of ventricles (ventricular tachyarrhythmia)
  • Atrial fibrillation and flutter and associated rapid heart rate (tachycardia)
  • Abnormally slow heart rate (bradycardia)
• Changes in blood pressure
• Fainting (syncope)
• Drug reaction with eosinophilia and systemic symptoms (DRESS)/multi-organ hypersensitivity

Common side effects of lacosamide include:

• Headache
• Drowsiness (somnolence)
• Tremor
• Balance disorder and gait disturbance (cerebellar syndrome)
• Fatigue
• Weakness (asthenia)
• Vertigo
• Chest pain
• Memory impairment
• Depression
• Uncontrolled eye movements (nystagmus)
• Double vision (diplopia)
• Blurred vision
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Dry mouth (xerostomia)
• Abnormal sensation in the mouth (oral paresthesia)
• Reduced sensation in the mouth (oral hypoesthesia)
• Contusion
• Bruising
• Skin laceration
• Itching (pruritus)
• Excessive sweating (hyperhidrosis)
• Injection site reactions including:
  • Pain
  • Irritation
  • Redness (erythema)
• Elevated liver enzymes
• Liver inflammation (hepatitis)
• Kidney inflammation (nephritis)
• Low count of red blood cells (anemia)
• Low count of neutrophil immune cells (neutropenia)
• Fever
• Irritability
• Feeling drunk
• Euphoria
• Ringing in the ears (tinnitus)
• Muscle spasms
• Fall
• Abnormal skin sensation (paresthesia)
• Reduced skin sensation (hypoesthesia)
• Cognitive disorder
• Disturbance in attention
• Speech disorder (dysarthria)
• Confusion
• Depressed or altered mood

Less common side effects of lacosamide include:

• Low count of granulocyte immune cells (agranulocytosis)
• Movement disorder (dyskinesia)
• New onset or worsening of seizures
• Severe skin reactions including:
  • Rash
  • Hives (urticaria)
  • Swelling beneath the skin and mucous membrane (angioedema)
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
• Aggression
• Agitation
• Hallucination
• Insomnia
• Psychotic disorder

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet: Schedule V

• 50 mg (Vimpat)
• 100 mg (Vimpat)
• 150 mg (Vimpat)
• 200 mg (Vimpat)

Capsule, extended-release: Schedule V

• 100 mg (Motpoly XR)
• 150 mg (Motpoly XR)
• 200 mg (Motpoly XR)

Injectable solution: Schedule V

• 200 mg/20 mL (Vimpat)

Oral solution: Schedule V

• 10 mg/mL (Vimpat)

Adult:

Partial Onset Seizures

• Indicated as monotherapy or adjunctive therapy for partial onset seizures

Monotherapy

• Vimpat
  • 100 mg oral/intravenous (IV) once every 12 hours initially, THEN, based on response and tolerability, increase dose at weekly intervals by 50 mg oral/IV twice daily; up to a recommended dose of 150-200 mg twice daily (300-400 mg/day) OR
  • Alternate initial loading dose schedule: 200 mg oral/IV as a single loading dose, followed 12 hours later by 100 mg oral/IV twice daily; THEN increase dose at weekly intervals by 50 mg twice daily; up to a recommended dose of 150-200 mg twice daily (300-400 mg/day)
• Motpoly XR
  • 200 mg orally once daily, THEN, based on response and tolerability, increase dose at weekly intervals by 100 mg orally once daily; up to a recommended dose of 300-400 mg/day

Adjunctive therapy

• Vimpat
  • Initial: 50 mg oral/IV once every 12 hours
  • Based on response and tolerability, increase dose at weekly intervals by 50 mg oral/IV twice daily; up to a recommended dose of 100-200 mg twice daily (200-400 mg/day)
• Motpoly XR
  • 100 mg orally once daily, THEN, based on response and tolerability, increase dose at weekly intervals by 100 mg orally once daily; up to a recommended dose of 200-400 mg/day

Conversion from single antiepileptic (AED) to lacosamide monotherapy

Vimpat

• Maintain lacosamide at recommended maintenance dose for at least 3 days before initiating withdrawal of the previous AED
• Patients currently treated with a single AED who will convert to lacosamide monotherapy, do not withdraw the concomitant AED until the therapeutic dosage of lacosamide is achieved and has been administered for at least 3 days
• Gradual withdrawal of initial AED over at least 6 weeks is recommended
• When discontinuing Vimpat, gradually withdraw treatment over at least 1 week is recommended

Motpoly XR

• Patients currently treated with a single AED who will convert to lacosamide monotherapy, do not withdraw the concomitant AED until the therapeutic dosage of lacosamide is achieved and has been administered for at least 4 days
• Gradual withdrawal of initial AED over at least 6 weeks is recommended
• When discontinuing extended-release lacosamide, a gradual withdrawal over at least 1 week is recommended

Primary Generalized Tonic-Clonic Seizures

Vimpat only

• Indicated as adjunctive therapy for primary generalized tonic-clonic seizures
• Initial: 50 mg oral/IV once every 12 hours
• Based on response and tolerability, increase dose at weekly intervals by 50 mg oral/IV twice daily; up to a recommended dose of 100-200 mg twice daily (200-400 mg/day)

Pediatric:

Partial Onset Seizures

• Indicated as monotherapy or adjunctive therapy for partial onset seizures
• Vimpat: Indicated as monotherapy or adjunctive therapy for partial-onset seizures in children aged 1 month or above
• Motpoly XR: Indicated as monotherapy or adjunctive therapy for partial onset seizures for pediatric patients weighing 50 kg or more
• Children below 1 month: Safety and efficacy not established

Children 1 month to 17 years

Weight below 6 kg

• Intravenous: 0.66 mg/kg three times daily, THEN, based on response and tolerability, increase dose at weekly intervals by 0.66 mg/kg three times daily; up to a recommended 2.5-5 mg/kg three times daily (7.5-15 mg/kg/day)
• Oral: 1 mg/kg twice daily (2 mg/kg/day), THEN, based on response and tolerability, increase dose at weekly intervals by 1 mg/kg twice daily (2 mg/kg/day), up to 3.75-7.5 mg/kg twice daily (7.5-15 mg/kg/day)
• Alternate initial dose: No loading dose, initiate 3.75 mg/kg orally twice daily or 2.5 mg/kg IV three times daily

Weight 6 to below 30 kg

• 1 mg/kg oral/IV twice daily, THEN, based on response and tolerability, increase dose at weekly intervals by 1 mg/kg oral/IV twice daily, up to recommended 3-6 mg/kg oral/IV twice daily (6-12 mg/kg/day)
• Alternate initial dose: 4.5 mg/kg oral/IV loading dose, THEN, 12 hours later initiate 3 mg/kg oral/IV twice daily

Weight 30 to below 50 kg

• 1 mg/kg oral/IV twice daily, THEN, based on response and tolerability, increase dose at weekly intervals by 1 mg/kg oral/IV twice daily, up to recommended 2-4 mg/kg oral twice daily (4-8 mg/kg/day)
• Alternate initial dose: 4 mg/kg oral/IV loading dose, THEN, 12 hours later initiate 2 mg/kg oral/IV twice daily

Weight 50 kg and above

• Vimpat
  • 50 mg oral/IV twice daily, THEN, based on response and tolerability, increase dose at weekly intervals by 50 mg oral/IV twice daily, up to recommended 150-200 mg oral/IV twice daily (300-400 mg/day) for monotherapy or 100-200 mg oral/IV twice daily (200-400 mg/day) for adjunctive therapy
  • Alternate initial dose: 200 mg oral/IV loading dose, THEN, 12 hours later initiate 2 mg/kg oral/IV twice daily
• Motpoly XR
  • Monotherapy: 100 mg orally once daily, THEN, based on response and tolerability, increase dose at weekly intervals by 100 mg orally once daily; up to a recommended dose of 300-400 mg/day
  • Adjunctive therapy: 100 mg orally once daily, THEN, based on response and tolerability, increase dose at weekly intervals by 100 mg orally once daily; up to a recommended dose of 200-400 mg/day

Conversion from single antiepileptic (AED) to lacosamide monotherapy

• Vimpat
  • Maintain lacosamide at recommended maintenance dose for at least 3 days before initiating withdrawal of the previous AED
  • Patients currently treated with a single AED who will convert to lacosamide monotherapy, do not withdraw the concomitant AED until the therapeutic dosage of lacosamide is achieved and has been administered for at least 3 days
  • Gradual withdrawal of initial AED over at least 6 weeks is recommended
  • When discontinuing Vimpat, gradually withdraw treatment over at least 1 week is recommended
• Motpoly XR
  • Patients currently treated with a single AED who will convert to lacosamide monotherapy, do not withdraw the concomitant AED until the therapeutic dosage of lacosamide is achieved and has been administered for at least 4 days
  • Gradual withdrawal of initial AED over at least 6 weeks is recommended
  • When discontinuing extended-release lacosamide, a gradual withdrawal over at least 1 week is recommended

Primary Generalized Tonic-Clonic Seizures

• Indicated as adjunctive therapy for primary generalized tonic-clonic seizures in patients aged 4 years or above with idiopathic generalized epilepsy
• Children below 4 years: Safety and efficacy not established

Children 4-17 years

• Weight 11 to below 30 kg
  • 1 mg/kg oral/IV twice daily, THEN, based on response and tolerability, increase dose at weekly intervals by 1 mg/kg oral/IV twice daily, up to recommended 3-6 mg/kg oral/IV twice daily (6-12 mg/kg/day)
  • Alternate initial dose: 4.5 mg/kg oral/IV loading dose, THEN, 12 hours later initiate 3 mg/kg oral/IV twice daily
• Weight 30 to below 50 kg
  • 1 mg/kg oral/IV twice daily, THEN, based on response and tolerability, increase dose at weekly intervals by 1 mg/kg oral/IV twice daily, up to recommended 2-4 mg/kg oral/IV twice daily (4-8 mg/kg/day)
  • Alternate initial dose: 4 mg/kg oral/IV loading dose, THEN, 12 hours later initiate 2 mg/kg oral/IV twice daily
• Weight 50 kg and above
  • 50 mg oral/IV twice daily, THEN, based on response and tolerability, increase dose at weekly intervals by 50 mg oral/IV twice daily, up to recommended 150-200 mg oral/IV twice daily (300-400 mg/day) for monotherapy or 100-200 mg oral/IV twice daily (200-400 mg/day) for adjunctive therapy
  • Alternate initial dose: 200 mg oral/IV loading dose, THEN, 12 hours later initiate 2 mg/kg oral/IV twice daily

Adult and Pediatric:

Dosage Modifications

Renal impairment

• Vimpat
  • In all patients with renal impairment, base dose initiation and titration on clinical response and tolerability
  • Mild to moderate (creatinine clearance [CrCl] 30 mL/minute or above): No dose adjustment necessary
  • Severe (CrCl below 30 mL/minute) or end-stage renal disease (ESRD): Reduce maximum dosage by 25%
  • Hemodialysis: Consider supplementing with up to 50% of dose after 4-hour dialysis session
  • Coadministration with strong CYP3A4 or CYP2C9 inhibitors: Lacosamide systemic exposure may increase; consider dose reduction
• Motpoly XR
  • In all patients with renal impairment, base dose initiation and titration on clinical response and tolerability
  • Mild to moderate (30 mL/minute or above): No dose adjustment necessary
  • Severe (CrCl below 30 mL/minute) or ESRD: Maximum recommended dosage is 300 mg/day
  • Hemodialysis: Consider supplementing with up to 50% of dose after 4-hour dialysis session
  • Coadministration with strong CYP3A4 or CYP2C9 inhibitors: Lacosamide systemic exposure may increase; consider dose reduction

Hepatic impairment

• Vimpat
  • Mild-to-moderate: Reduce maximum dosage by 25%; observe closely for adverse reactions, and base dose initiation and titration on clinical response and tolerability
  • Severe: Not recommended
  • Coadministration with strong CYP3A4 or CYP2C9 inhibitors: Lacosamide systemic exposure may increase; consider dose reduction
• Motpoly XR
  • Mild-to-moderate: Maximum recommended dosage is 300 mg/day; observe closely for adverse reactions, and base dose initiation and titration on clinical response and tolerability
  • Severe: Not recommended
  • Coadministration with strong CYP3A4 or CYP2C9 inhibitors: Lacosamide systemic exposure may increase; consider dose reduction

Dosing Considerations

• IV administration indicated as short-term replacement (up to 5 consecutive days) when oral administration is not feasible

Addiction/overdose

• Lacosamide did not produce any physical withdrawal symptoms in clinical trials, however, it produced euphoria, and psychological dependence is possible.
• Lacosamide overdose can cause nausea, dizziness, seizures, including generalized tonic-clonic seizures and status epilepticus, decreased level of consciousness, confusion, cardiac conduction disorders, cardiogenic shock, cardiac arrest, coma and death.
• There is no specific antidote to lacosamide. Overdose is treated with symptomatic and supportive measures including monitoring of vital signs and hemodialysis, if required, particularly in patients with impaired kidney function.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Lacosamide has no known severe interactions with other drugs.
• Serious interactions of lacosamide include:
  • abametapir
  • apalutamide
  • fexinidazole
  • idelalisib
  • ivosidenib
  • metoclopramide intranasal
  • olopatadine intranasal
  • tucatinib
  • voxelotor
• Lacosamide has moderate interactions with at least 66 different drugs.
• Lacosamide has mild interactions with at least 22 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There is insufficient information to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes with the use of lacosamide in pregnant women, however, animal reproductive studies show it can cause fetal harm (neurotoxicity) if used during pregnancy.
• Data from published literature show that lacosamide is present in breastmilk and can increase sleepiness in breastfed infants, however, its effects on milk production is not known.
• Decision to breastfeed must be made considering the importance of lacosamide to the nursing mother, and the risks to the infant from exposure to the drug or the mother’s underlying condition. Breastfed infants must be monitored for excessive sedation, if a nursing mother takes lacosamide.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as lacosamide, during pregnancy. Women taking lacosamide during pregnancy should be encouraged to enroll in the North American Antiepileptic Drug (NAAED Pregnancy Registry) by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.

• Take lacosamide exactly as directed. Do not abruptly discontinue the medication, it should be tapered under your physician’s guidance.
• Lacosamide may induce or worsen depression and suicidal thoughts and behavior. Seek support from family, friends and your healthcare provider if you feel depressed.
• If you are a family member or caregiver of a patient taking lacosamide, be alert for signs and symptoms of depression in the patient and contact the treating physician if you notice unusual changes in the patient’s mood or behavior.
• Lacosamide may cause dizziness, double vision and drowsiness, and affect balance and coordination. Avoid hazardous activities such as driving and operating heavy machinery until the drug’s effects can be determined.
• Lacosamide can cause irregular heart rhythm and fainting, particularly in people with pre-existing heart disease or those taking medication that affect the heart. Report to your physician immediately if you experience any heart-related symptoms. If you feel faint, lie down with raised legs and call or have someone call your physician.
• Contact your physician immediately if you experience symptoms of multi-organ hypersensitivity known as drug reaction with eosinophilia and systemic symptoms (DRESS), which may include fever, rash, lymph node swelling, facial swelling, as well as symptoms related to the liver such as fatigue, dark urine or jaundice, or other symptoms related to the kidney or any other organ.
• Store lacosamide safely out of reach of children.
• In case of overdose, seek immediate medical help or contact Poison Control.