LACOSAMIDE

LACOSAMIDE — lacosamide injection
XLCare Pharmaceuticals Inc.

1 INDICATIONS AND USAGE

1.1 Partial-Onset Seizures

Lacosamide injection is indicated for the treatment of partial-onset seizures in patients 17 years of age and older. Pediatric use information is approved for UCB, Inc.’s VIMPAT ^® (lacosamide) injection. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information

2 DOSAGE AND ADMINISTRATION

2.1 Dosage Information

The recommended dosage for monotherapy and adjunctive therapy for partial-onset seizures in 17 years of age and older is included in Table 1. 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. Table 1: Recommended Dosages for Partial-Onset Seizures (Monotherapy or Adjunctive Therapy) in Patients 17 years of Age and older*

Age and Body Weight	Initial Dosage	Titration Regimen	Maintenance Dosage
Adults (17 years and older)	Monotherapy ** : 100 mg twice daily (200 mg per day) Adjunctive Therapy: 50 mg twice daily (100 mg per day)	Increase by 50 mg twice daily (100 mg per day) every week	Monotherapy ** : 150 mg to 200 mg twice daily (300 mg to 400 mg per day) Adjunctive Therapy: 100 mg to 200 mg twice daily (200 mg to 400 mg per day)
	Alternate Initial Dosage: 200 mg single loading dose, followed 12 hours later by 100 mg twice daily

*when not specified, the dosage is the same for monotherapy for partial-onset seizures and adjunctive therapy for partial-onset seizures.
**Monotherapy for partial-onset seizures only

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 [see Adverse Reactions ( 6.1) and Clinical Studies ( 14.2)].

Lacosamide Injection Dosage

Lacosamide injection may be used when oral administration is temporarily not feasible [see Dosage and Administration ( 2.6) and Warnings and Precautions ( 5.3)]. Lacosamide injection can be administered intravenously to adult patients with the same dosing regimens described for oral dosing.
The clinical study experience of intravenous lacosamide is limited to 5 days of consecutive treatment.
Loading Dose in Adult Patients (17 Years and Older)
Lacosamide injection 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).
The maintenance dose regimen should be continued for one week. Lacosamide injection 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 [see Adverse Reactions ( 6.1) and Clinical Pharmacology ( 12.3)].

The use of a loading dose in pediatric patients has not been studied.

Pediatric use information is approved for UCB, Inc.’s VIMPAT ^® (lacosamide) injection. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.2 Converting From a Single Antiepileptic (AED) to Lacosamide Injection Monotherapy for the Treatment of Partial-Onset Seizures

For patients who are already on a single AED and will convert to lacosamide injection monotherapy, withdrawal of the concomitant AED should not occur until the therapeutic dosage of lacosamide injection 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.

2.3 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 (CL _CR ) less than 30 mL/min as estimated by the Cockcroft-Gault equation for adults; CL _CR less than 30 ml/min/1.73m ² 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 injection 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 [see Drug Interactions ( 7.1), Use in Specific Populations ( 8.6), and Clinical Pharmacology ( 12.3)].

2.4 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 injection 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 [see Drug Interactions ( 7.1), Use in Specific Populations ( 8.7), and Clinical Pharmacology ( 12.3)].

2.6 Preparation and Administration Information for Lacosamide Injection

Preparation
Lacosamide injection can be administered intravenously without further dilution or may be mixed with diluents listed below. The diluted solution should not be stored for more than 4 hours at room temperature.
Diluents:

Sodium Chloride Injection 0.9% (w/v)
Dextrose Injection 5% (w/v)
Lactated Ringer’s Injection

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Product with particulate matter or discoloration should not be used.
Lacosamide injection is for single-dose only. Any unused portion of lacosamide injection should be discarded.
Administration
The recommended infusion duration is 30 to 60 minutes; however, infusions as rapid as 15 minutes can be administered in adults if required [see Adverse Reactions ( 6.1) and Clinical Pharmacology ( 12.3)]. Infusion durations less than 30 minutes are generally not recommended in pediatric patients [see Adverse Reactions ( 6.1)].
Intravenous infusion of lacosamide may cause bradycardia, AV blocks, and ventricular tachyarrhythmia [see Warnings and Precautions ( 5.3)]. Obtaining an ECG before beginning lacosamide injection and after lacosamide injection is titrated to steady-state maintenance dose is recommended in patients with underlying proarrhythmic conditions or on concomitant medications that affect cardiac conduction [see Drug Interactions ( 7.2)].
Storage and Stability
The diluted solution should not be stored for more than 4 hours at room temperature. Any unused portion of lacosamide injection should be discarded.