Lacosamide (Vimpat) is an anticonvulsant drug that is used in the treatment of partial-onset seizures and patients with painful diabetic neuropathy.

Lacosamide (Vimpat) Uses:

• Focal (partial) onset seizures:

  • Treating seizures in kids 4 years and older and adults, either alone or along with other treatments.

• Off Label Use of Lacosamide in Adults:

  • Refractory status epilepticus means that seizures keep happening despite treatment with medications.
  • People sometimes use pregabalin for painful diabetic neuropathy even though it's not officially approved for that use.
  • But experts suggest not using it for this because other medications like pregabalin and duloxetine work better as the first choice.

Lacosamide (Vimpat) Dose in Adults:

Lacosamide (Vimpat) Dose in the Focal (partial) onset seizure:

• Monotherapy: Oral, IV:

  • Start with 100 mg twice a day.

  • Depending on how you respond to it and if you can tolerate it, the dose might go up by 50 mg twice a day each week.

  • Alternative initial dosage:
    • Take 200 mg as a loading dose first, then 100 mg twice daily for a week.
    • After that, depending on how well you handle it and how it works for you, the dose might increase by 50 mg twice daily every week.
    • Remember, when taking loading doses, it's important to have medical supervision because there's a higher chance of CNS adverse reactions.
  • Maintenance:

    • Some people start with 150 to 200 mg twice daily.

    • If needed, the dose might go up to 300 mg twice daily for the best outcomes.

Note:

• If you're already taking another antiepileptic and switching to lacosamide alone, keep taking the maintenance dose for 3 days before starting to reduce the other antiepileptic.
• Slowly decrease the other antiepileptic over at least 6 weeks.

• Adjunctive therapy: Oral, IV:

  • Initial:

    • Start with 50 mg twice daily.

    • Depending on how you respond to it and if you can tolerate it, the dose might increase by 50 mg twice daily each week.

  • Alternative initial dosage:

    • First, take a loading dose of 200 mg.

    • Then, about 12 hours later, take 100 mg twice daily for a week.

    • Depending on how you react to it and if you can tolerate it, the dose might increase by 50 mg twice daily each week.

    • Remember, when taking loading doses, it's important to have medical supervision because there's a higher chance of CNS adverse reactions.

  • Maintenance dose:
  • Take between 100 to 200 mg twice daily.

Note:

• According to studies with oral forms, some people might benefit from doses up to 600 mg per day, especially if they experience subsequent generalized tonic-clonic seizures.

• However, it's important to note that the risk of side effects increases at higher doses.

Lacosamide (Vimpat) Dose in Refractory Status epilepticus (off-label):

• Initially, through IV, you might receive 200 to 400 mg.
• After that, you might continue with 200 to 400 mg divided into two doses per day for maintenance.
• In some cases, the dose might go up to 600 mg per day for the best results.

Note:

• The Neurocritical Care Society suggests giving 200 mg over 15 minutes.
• However, some experts give IV doses up to 400 mg either through a push or infusion, but at a rate of no more than 80 mg per minute.

• Dosing conversion:

  • Between oral and IV dosing:

    • Switch to IV therapy temporarily using the same total daily dose.

    • Remember, clinical trials have only tested consecutive IV lacosamide treatment for up to 5 days.

• Discontinuation of therapy:

  • If someone has been taking lacosamide for a long time, and there are no urgent safety concerns, it's best to slowly stop taking it over a few weeks to several months.
  • This helps reduce the risk of seizures or other withdrawal symptoms.

Lacosamide (Vimpat) Dose in Childrens:

Lacosamide (Vimpat) Dose in Partial-Onset Seizures:

Note:

• If a patient is already taking only one antiepileptic and switching to lacosamide alone, keep taking the maintenance dose for 3 days before starting to reduce the other antiepileptic.
• Slowly decrease the other antiepileptic over at least 6 weeks.

• Children ≥4 to 17 years:

  • Monotherapy and adjunctive therapy:

    • For patients weighing 11 to less than 30 kg:

    • Start with 1 mg/kg/dose twice daily.
    • Depending on how they respond and tolerate it, increase the dose by 1 mg/kg/dose twice daily each week.
    • Maintenance dose: 3 to 6 mg/kg/dose twice daily.

    • For patients weighing 30 to less than 50 kg:

    • Start with 1 mg/kg/dose twice daily.
    • Depending on how they respond and tolerate it, increase the dose by 1 mg/kg/dose twice daily each week.
    • Maintenance dose: 2 to 4 mg/kg/dose twice daily.

    • For patients weighing 50 kg or more:

    • Initial dose (for both alone and with other drugs): 50 mg twice daily.
    • Depending on how they respond and tolerate it, increase the dose by 50 mg twice daily each week.
    • Maintenance dose:
      • For using lacosamide alone: 150 to 200 mg twice daily.
      • For using lacosamide with other drugs: 100 to 200 mg twice daily.

Note: In trials with adults using lacosamide along with other drugs, doses higher than 400 mg per day didn't show more effectiveness and led to more side effects.

• Adolescents ≥17 years:

Note:

• When switching from oral to IV formulations, keep the total daily dose and frequency the same.

• IV therapy should only be considered as a last option.

• Also, it's important to note that clinical studies have only tested consecutive IV lacosamide treatment for up to 5 days.

  • Monotherapy: Oral, IV:

    • Initial:
      • Take 100 mg twice a day.
      • Depending on how you respond to it and if you can handle it well, the dose might go up by 50 mg twice a day each week.
    • Alternate initial dosage:
      • First, take a loading dose of 200 mg, then approximately 12 hours later, start taking 100 mg twice daily for a week.
      • Depending on how well you respond to it and if you can tolerate it, the dose might increase by 50 mg twice daily at weekly intervals.
      • Remember, when taking loading doses, it's important to have medical supervision because there's a higher chance of CNS adverse reactions.
    • Maintenance:
      • Take between 150 to 200 mg twice daily.
      • It's important to note that in clinical trials where lacosamide was used along with other treatments in adults, doses higher than 400 mg per day didn't show more effectiveness and led to more side effects.

  • Adjunctive therapy: Oral, IV:

    • Initial:
      • Begin with 50 mg twice daily.
      • Depending on how you respond to it and if you can tolerate it, the dose might increase by 50 mg twice daily each week.
    • Alternative initial dosage:
      • Start with a loading dose of 200 mg, then approximately 12 hours later, take 100 mg twice daily for a week.
      • Depending on how well you respond to it and if you can tolerate it, the dose might increase by 50 mg twice daily at weekly intervals.

Note:  It's crucial to have medical supervision when giving loading doses because there's a higher chance of CNS adverse reactions.

• Maintenance dose:

  • Take between 100 to 200 mg twice daily.

  • It's important to note that in clinical trials where lacosamide was used along with other treatments in adults, doses higher than 400 mg per day didn't show more effectiveness and led to more adverse reactions.

Lacosamide (Vimpat) Dose in Severe and Refractory Seizures: 

• Infants ≥6 months, Children, and Adolescents <17 years:

  • Oral: Initial:
    • Start with 1 to 2 mg/kg/day divided into two doses per day, with the typical maximum initial dose being 50 mg per dose.
    • You can adjust the dose by 1 to 2 mg/kg/day every week until you achieve the desired effect.
    • The range of reported mean maintenance doses is between 4.7 to 15.2 mg/kg/day.

Lacosamide (Vimpat) Pregnancy Risk Category: C

• Lacosamide can pass from the mother to the baby during pregnancy.
• Pregnancy-related changes in the body may affect how lacosamide works.
• We don't have much information about pregnancy outcomes when mothers use lacosamide.
• If a pregnant woman needs an antiepileptic, it's best to use only one medication at the lowest effective dose to reduce the risk of birth defects.
• Babies born to mothers taking antiepileptic medications might have a higher chance of having problems after birth.

Use of lacosamide while breastfeeding

• Lacosamide can be found in breast milk.
• There's a case where a breastfeeding baby, whose mother took lacosamide along with other medications during pregnancy and after birth, showed symptoms like drowsiness and poor nutrition.
• The manufacturer recommends considering both the risks to the baby and the benefits to the mother when deciding whether to continue breastfeeding during lacosamide therapy.

Lacosamide (Vimpat) Dose in Kidney Disease:

Patients with a creatinine clearance (CrCl) of 30 mL/minute or higher generally don't need a dosage adjustment.

However, if they have severe kidney problems and are taking strong CYP3A4 or CYP2C9 inhibitors, a dose reduction may be necessary.

For patients with a CrCl of exactly 30 mL/minute, the dose should be reduced to 75% of the maximum dose.

Further dosage reduction or limitation may be needed if they are also taking strong CYP3A4 or CYP2C9 inhibitors.

For patients with end-stage renal disease (ESRD) requiring hemodialysis, the dose should be limited to 75% of the maximum dosage.

Additionally, if they are using strong CYP3A4 or CYP2C9 inhibitors, further dosage reduction or limitation may be necessary.

During hemodialysis treatment, a supplemental dose of 50% can be considered after a 4-hour session to account for drug removal during the procedure.

Lacosamide (Vimpat) Dose in Liver disease:

• Mild to moderate hepatic impairment:
  • If patients are taking powerful CYP3A4 and/or CYP2C9 inhibitors along with lacosamide, they should reduce their dose to 75% of the maximum dose.
  • They may also need to further reduce or limit their dosage based on their individual circumstances and the advice of their healthcare provider.
• Severe hepatic impairment:
  • Using lacosamide is not recommended in patients taking powerful CYP3A4 and/or CYP2C9 inhibitors.

Side Effects of Lacosamide (Vimpat):

• Central nervous system:

  • Headache
  • Dizziness

• Gastrointestinal:

  • Nausea

Less Common Side Effects of Lacosamide (Vimpat):

• Central Nervous System:

  • Vertigo
  • Fatigue
  • Equilibrium Disturbance
  • Ataxia
  • Abnormal Gait
  • Depression
  • Drowsiness

• Dermatologic:

  • Pruritus

• Gastrointestinal:

  • Vomiting
  • Diarrhea

• Hematologic & Oncologic:

  • Bruise

• Local:

  • Pain At Injection Site
  • Local Irritation

• Neuromuscular & Skeletal:

  • Tremor
  • Asthenia

• Ophthalmic:

  • Diplopia
  • Blurred Vision
  • Nystagmus

• Miscellaneous:

  • Laceration

Rare side effects of Lacosamide (Vimpat):

• Cardiovascular:

  • Palpitations
  • Syncope

• Central Nervous System:

  • Cerebellar Syndrome
  • Cognitive Dysfunction
  • Confusion
  • Disturbance In Attention
  • Dysarthria
  • Falling
  • Hypoesthesia
  • Intoxicated Feeling
  • Irritability
  • Mood Changes
  • Paresthesia
  • Suicidal Ideation
  • Suicidal Tendencies

• Gastrointestinal:

  • Constipation
  • Dyspepsia
  • Oral Hypoesthesia
  • Xerostomia

• Hematologic & Oncologic:

  • Anemia
  • Neutropenia

• Neuromuscular & Skeletal:

  • Muscle Spasm

• Otic:

  • Tinnitus

• Miscellaneous:

  • Fever

Contraindications to Lacosamide (Vimpat):

US labeling:

• No contraindications listed on label.

Canadian labeling:

• Lacosamide should not be used in individuals who have had a hypersensitivity reaction to any component of lacosamide or who have a history of second- or third-degree atrioventricular block.

Warnings and precautions

• Cardiovascular effects

  • Lacosamide can cause prolongation of the PR interval and may lead to cardiac arrhythmias such as bradycardia, atrioventricular (AV) block, and ventricular tachyarrhythmias.

  • In rare cases, these events have resulted in cardiac arrest, death, or asystole.

  • Patients with conditions predisposing them to arrhythmias, such as underlying cardiac issues or use of medications affecting cardiac conduction, are at higher risk.

  • Special care should be taken with patients having cardiac conduction issues like first- or second-degree atrioventricular blocks, sick sinus syndrome with pacemaker, sodium channelopathies, myocardial ischemia, heart failure, or those using medications affecting cardiac conduction and prolonging PR intervals.

  • Before starting lacosamide therapy or when reaching the steady-state maintenance dose, an ECG should be performed in these patients.

  • During IV administration, close monitoring is necessary as bradycardia, AV block, and ventricular tachyarrhythmias may occur.

  • Patients experiencing symptoms such as a low or irregular pulse, dizziness, or fainting should seek immediate medical attention.

  • In short-term trials, patients with diabetes and/or heart disease showed slightly more frequent occurrences of syncope or atrial fibrillation/flutter.

  • Open-label studies indicated that syncope was associated with a history of heart disease risk factors and drugs that slow AV conduction.

• CNS effects

  • During lacosamide therapy, patients may experience dizziness or ataxia.

  • Therefore, they should exercise caution when driving or operating machinery that requires alertness.

• Multiorgan hypersensitivity reactions (drug response with eosinophilia or systemic symptoms [DRESS]).

  • Lacosamide and other antiepileptic medications have been linked to rare but serious multiorgan hypersensitivity reactions that can be life-threatening.
  • Patients should be monitored for signs of lymphatic, hepatic, and renal disorders while taking lacosamide.
  • If such manifestations occur, transitioning to an alternative therapy or gradual discontinuation of lacosamide may be necessary.

• Ophthalmic effects

  • Lacosamide therapy may lead to blurred vision or double vision (diplopia).
  • Patients experiencing persistent visual impairments should undergo further evaluation.
  • Those with preexisting vision-related conditions should be monitored more closely while on lacosamide treatment.

• Suicidal thoughts:

  • A pooled analysis of trials involving various antiepileptic medications, regardless of their intended use, showed an increased risk of suicidal thoughts or behaviors.

  • Patients receiving treatment had an incidence rate of 0.43%, compared to 0.2% for those receiving a placebo.

  • This risk can appear as early as one week after starting the trial and may persist throughout its duration, with most trials lasting less than 24 weeks.

  • It's important to be vigilant for any changes in behavior or thoughts that could indicate depression or suicidal tendencies.

  • If you notice such symptoms, inform your healthcare provider immediately.

• Hepatic impairment

  • Patients with severe hepatic impairment should avoid using this product.

  • For patients using potent CYP3A4 or CYP2C9 inhibitors and also experiencing hepatic impairment, dosage adjustments may be necessary.

• Renal impairment

  • Patients with severe renal impairment should exercise caution when using this product.

  • Dosage adjustment is necessary for patients with a creatinine clearance (CrCl) of less than 30 mL/minute.

  • Supplementation may also be required for patients undergoing hemodialysis.

  • Furthermore, patients with any level of renal impairment may need to adjust their dosages if they are taking strong CYP3A4 or CYP2C9 inhibitors.

Lacosamide: Drug Interaction

Monitoring parameters:

• Patients with severe conduction problems, sodium channelopathies, or those taking medications that affect cardiac conduction or prolong the PR interval should undergo an ECG tracing before starting lacosamide therapy.

• Close monitoring is necessary during IV infusions as bradycardia, AV block, and ventricular tachyarrhythmias may occur.

• Additionally, monitoring for suicidality, including suicidal thoughts, depression, and behavioral changes, is essential during lacosamide therapy.

• Any concerning symptoms should be promptly reported to healthcare providers for appropriate management.

How to administer Lacosamide (Vimpat)?

IV:

• Infusion:

  • Lacosamide can be administered intravenously over 15 to 60 minutes, with infusions over 30 to 60 minutes preferred to minimize adverse effects.

  • IV administration has been used for up to 5 days.

  • It can be administered without further dilution or may be mixed with compatible diluents such as normal saline (NS), lactated Ringer's (LR), or dextrose 5% in water (D5W).

• Bolus (off label):

  • Doses of up to 400 mg of lacosamide may be administered undiluted at a rate of no more than 80 mg per minute.

Oral solution, tablets:

• Lacosamide can be taken with or without food.

• When using the oral solution, it should be measured with a calibrated device, not a household teaspoon or tablespoon.

• The oral solution can also be given through a nasogastric or gastrostomy tube.

• Tablets should be swallowed whole and should not be divided.

Mechanism of action of Lacosamide (Vimpat):

• According to in vitro research, lacosamide can stabilize hyperexcitable neuronal membranes, preventing recurrent neuronal firing.
• It accomplishes this by improving delayed inactivation sodium channels.
• However, it has no effect on fast inactivation sodium channels.

Absorption:

• Oral: Completely

Protein binding:

• Lacosamide has a protein binding of less than 15%.

Metabolism:

• Lacosamide is metabolized in the liver primarily by enzymes CYP3A4, CYP2C9, and CYP2C19.
• One of its metabolites is O-desmethyllacosamide, which is inactive.

Bioavailability:

• The bioavailability of lacosamide is approximately 100%, meaning that almost all of the administered dose reaches the systemic circulation unchanged.

Half-life elimination:

• In children aged 4 years and above, as well as adolescents:

• For a mean weight of 11 kg, lacosamide has a half-life of 7.4 hours.
• For a mean weight of 28.9 kg, the half-life is 10.6 hours.
• For a mean weight of 70 kg, the half-life is 14.8 hours.

• In adults, the half-life of lacosamide is approximately 13 hours.

• The time to reach peak plasma concentration after oral administration of lacosamide is typically between 1 to 4 hours.
• Lacosamide is primarily excreted in the urine, with approximately 95% of the dose being eliminated this way.
• Within the urine, about 40% is excreted as unchanged drug, 30% as an inactive metabolite, and 20% as an uncharacterized metabolite.
• Only a small fraction of the dose (less than 0.5%) is excreted in the feces.

International Brand Names of Lacosamide:

• Vimpat
• APO-Lacosamide
• Auro-Lacosamide
• MAR-Lacosamide
• MINT-Lacosamide
• Pharma-Lacosamide
• SANDOZ Lacosamide
• TEVA-Lacosamide
• Vimpat
• Aldinam
• Andovimpamide
• Copinate
• Cosamide
• Fedolacosa
• Lacasa
• Lacosam
• Lacosamet
• Lacoset
• Lacotem
• Lacovimp

Lacosamide Brand Names in Pakistan: