Lacasa 50/Lacasa 100/Lacasa 150

Lacosamide.

Lacasa 50: Each film coated tablet contains: Lacosamide 50 mg.
Lacasa 100: Each film coated tablet contains: Lacosamide 100 mg.
Lacasa 150: Each film coated tablet contains: Lacosamide 150 mg.
The chemical name of lacosamide, the single (R)-enantiomer, is (R)-2-acetamido-N-benzyl-3-methoxypropionamide (IUPAC). Lacosamide is a functionalized amino acid. Its molecular formula is C₁₃H₁₈N₂O₃ and its molecular weight is 250.30.

Pharmacotherapeutic group: antiepileptics, other antiepileptics. ATC code: N03AX18.
Pharmacology: Pharmacodynamics and Pharmacokinetics: Mechanism of action: The active substance, lacosamide (R-2-acetamido-N-benzyl-3-methoxypropionamide) is a functionalised amino acid.
The precise mechanism by which lacosamide exerts its antiepileptic effect in humans remains to be fully elucidated. In vitro electrophysiological studies have shown that lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes.
Pharmacodynamic effects: Lacosamide protected against seizures in a broad range of animal models of partial and primary generalised seizures and delayed kindling development.
In non-clinical experiments lacosamide in combination with levetiracetam, carbamazepine, phenytoin, valproate, lamotrigine, topiramate or gabapentin showed synergistic or additive anticonvulsant effects.

Lacosamide is indicated for the treatment of partial-onset seizures (monotherapy or adjunctive therapy) and as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older.

The recommended dosage for adults and pediatric patients 4 years to less than 17 years of age is included in Table 1. In pediatric patients 4 years to less than 17 years of age, the recommended dosing regimen is dependent upon body weight. Dosage should be increased based on clinical response and tolerability, no more frequently than once per week. Titration increments should not exceed those shown in Table 1. (See Table 1.)

Click on icon to see table/diagram/image

In adjunctive clinical trials in adult patients with partial-onset seizures, a dosage higher than 200 mg twice daily (400 mg per day) was not more effective and was associated with a substantially higher rate of adverse reactions.
Loading Dose in Adult Patients (17 Years and Older): Lacosamide may be initiated in adult patients with a single loading dose of 200 mg, followed approximately 12 hours later by 100 mg twice daily (200 mg per day). This maintenance dose regimen should be continued for one week. Lacosamide can then be titrated as recommended in Table 1. The adult loading dose should be administered with medical supervision because of the increased incidence of CNS adverse reactions.
The use of a loading dose in pediatric patients has not been studied.
Converting From a Single Antiepileptic (AED) to LACOSAMIDE Monotherapy for the Treatment of Partial-Onset Seizures: For patients who are already on a single AED and will convert to Lacosamide monotherapy, withdrawal of the concomitant AED should not occur until the therapeutic dosage of Lacosamide is achieved and has been administered for at least 3 days. A gradual withdrawal of the concomitant AED over at least 6 weeks is recommended.
Dosage Information for Patients with Renal Impairment: For patients with mild to moderate renal impairment, no dosage adjustment is necessary.
For patients with severe renal impairment [creatinine clearance (CLCR) less than 30 mL/min as estimated by the Cockcroft-Gault equation for adults; CLCR less than 30 mL/min/1.73 m² as estimated by the Schwartz equation for pediatric patients] or end-stage renal disease, a reduction of 25% of the maximum dosage is recommended.
In all patients with renal impairment, the dose titration should be performed with caution.
Hemodialysis: LACOSAMIDE is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment, dosage supplementation of up to 50% should be considered.
Concomitant Strong CYP3A4 or CYP2C9 Inhibitors: Dose reduction may be necessary in patients with renal impairment who are taking strong inhibitors of CYP3A4 and CYP2C9.
Dosage Information for Patients with Hepatic Impairment: For patients with mild or moderate hepatic impairment, a reduction of 25% of the maximum dosage is recommended. The dose titration should be performed with caution in patients with hepatic impairment.
Lacosamide use is not recommended in patients with severe hepatic impairment.
Concomitant Strong CYP3A4 and CYP2C9 Inhibitors: Dose reduction may be necessary in patients with hepatic impairment who are taking strong inhibitors of CYP3A4 and CYP2C9.
Discontinuation of Lacosamide: When discontinuing Lacosamide, a gradual withdrawal over at least 1 week is recommended.
Method of administration: Lacosamide film-coated tablets are for oral use. Lacosamide may be taken with or without food.

Symptoms: Symptoms observed after an accidental or intentional overdose of lacosamide are primarily associated with CNS and gastrointestinal system.
The types of adverse reactions experienced by patients exposed to doses above 400 mg up to 800 mg were not clinically different from those of patients administered recommended doses of lacosamide.
Reactions reported after an intake of more than 800 mg are dizziness, nausea, vomiting, seizures (generalised tonic-clonic seizures, status epilepticus). Cardiac conduction disorders, shock and coma have also been observed. Fatalities have been reported in patients following an intake of acute single overdose of several grams of lacosamide.
Management: There is no specific antidote for overdose with lacosamide. Treatment of lacosamide overdose should include general supportive measures and may include haemodialysis if necessary.

Hypersensitivity to the active substance or to any of the excipients: Microcrystalline cellulose, Crospovidone, Hydroxypropyl cellulose, Silica colloidal anhydrous, Magnesium stearate.
Known second- or third-degree atrioventricular (AV) block.

Suicidal ideation and behaviour: Suicidal ideation and behaviour have been reported in patients treated with antiepileptic medicinal products in several indications. A meta-analysis of randomised placebo-controlled trials of antiepileptic medicinal products has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for lacosamide.
Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
Cardiac rhythm and conduction: Dose-related prolongations in PR interval with lacosamide have been observed in clinical studies. Lacosamide should be used with caution in patients with known conduction problems, severe cardiac disease (e.g. history of myocardial infarction or heart failure), in elderly patients, or when lacosamide is used in combination with products known to be associated with PR prolongation.
In these patients it should be considered to perform an ECG before a lacosamide dose increase above 400 mg/day and after lacosamide is titrated to steady-state.
Second-degree or higher AV block has been reported in post-marketing experience. In the placebo-controlled trials of lacosamide in epilepsy patients, atrial fibrillation or flutter were not reported; however, both have been reported in open-label epilepsy trials and in post-marketing experience.
Patients should be made aware of the symptoms of second-degree or higher AV block (e.g. slow or irregular pulse, feeling of lightheaded and fainting) and of the symptoms of atrial fibrillation and flutter (e.g. palpitations, rapid or irregular pulse, shortness of breath). Patients should be counselled to seek medical advice should any of these symptoms occur.
Dizziness: Treatment with lacosamide has been associated with dizziness which could increase the occurrence of accidental injury or falls. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicine.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has been reported in patients taking antiepileptic drugs, including lacosamide. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection.
Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Lacosamide should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
Risks in Patients with Phenylketonuria: Phenylalanine can be harmful in patients with phenylketonuria (PKU). Lacosamide oral solution contains aspartame, a source of phenylalanine. A 200 mg dose of lacosamide oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine. Before prescribing lacosamide oral solution to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including lacosamide oral solution.

Pregnancy: Risk related to epilepsy and antiepileptic medicinal products in general: For all antiepileptic medicinal products, it has been shown that in the offspring of treated women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population. In the treated population, an increase in malformations has been noted with polytherapy, however, the extent to which the treatment and/or the illness is responsible has not been elucidated.
Moreover, effective antiepileptic therapy must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.
Risk related to lacosamide: There are no adequate data from the use of lacosamide in pregnant women. Studies in animals did not indicate any teratogenic effects in rats or rabbits, but embryotoxicity was observed in rats and rabbits at maternal toxic doses. 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 women decide to become pregnant, the use of this product should be carefully re-evaluated.
Breastfeeding: It is unknown whether lacosamide is excreted in human breast milk. A risk to the newborns/infants cannot be excluded. Animal studies have shown excretion of lacosamide in breast milk. For precautionary measures, breast-feeding should be discontinued during treatment with lacosamide.

Summary of safety profile: Based on the analysis of pooled placebo-controlled clinical trials in adjunctive therapy in 1,308 patients with partial-onset seizures, a total of 61.9% of patients randomised to lacosamide and 35.2% of patients randomised to placebo reported at least 1 adverse reaction. The most frequently reported adverse reactions (≥ 10%) with lacosamide treatment were dizziness, headache, nausea and diplopia. They were usually mild to moderate in intensity. Some were dose-related and could be alleviated by reducing the dose. Incidence and severity of central nervous system (CNS) and gastrointestinal (GI) adverse reactions usually decreased over time.
In all of these controlled studies, the discontinuation rate due to adverse reactions was 12.2% for patients randomised to lacosamide and 1.6% for patients randomised to placebo. The most common adverse reaction resulting in discontinuation of lacosamide therapy was dizziness.
Incidence of CNS adverse reactions such as dizziness may be higher after a loading dose.
Based on the analysis of data from a non-inferiority monotherapy clinical trial comparing lacosamide to carbamazepine controlled release (CR), the most frequently reported adverse reactions (≥ 10%) for lacosamide were headache and dizziness. The discontinuation rate due to adverse reactions was 10.6% for patients treated with lacosamide and 15.6% for patients treated with carbamazepine CR.
Tabulated list of adverse reactions: The table as follows shows the frequencies of adverse reactions which have been reported in clinical trials and post-marketing experience. The frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and not known (frequency cannot be estimated from available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table 2.)

Click on icon to see table/diagram/image

Lacosamide should be used with caution in patients treated with medicinal products known to be associated with PR prolongation (e.g. carbamazepine, lamotrigine, eslicarbazepine, pregabalin) and in patients treated with class I antiarrhythmics. However, subgroup analysis did not identify an increased magnitude of PR prolongation in patients with concomitant administration of carbamazepine or lamotrigine in clinical trials.

Store at temperatures not exceeding 30°C.

Anticonvulsants

N03AX18 - lacosamide ; Belongs to the class of other antiepileptics.

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