VIMPAT® DOSING
VIMPAT DOSING IN ADULTS
Monotherapy Dosing* Adjunctive Therapy Dosing 200 mg Loading Dose For Adults IV and Oral Solution Dosing Select Dosing in Special Populations
INDICATION
VIMPAT® is indicated for the treatment of partial-onset seizures in patients 4 years of age and older.
VIMPAT is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older.
IMPORTANT SAFETY INFORMATION
VIMPAT is associated with important warnings and precautions including suicidal behavior and ideation, dizziness and ataxia, cardiac rhythm and conduction abnormalities, syncope, and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity.
Partial-Onset Seizures
In the adult adjunctive placebo-controlled trials for partial-onset seizures, the most common
adverse reactions (≥10% and greater than placebo) were dizziness, headache, nausea, and diplopia.
In the adult monotherapy clinical trial, adverse reactions were generally similar to those observed
and attributed to drug in adjunctive placebo-controlled trials, with the exception of insomnia
(observed at a higher rate of ≥2%). Pediatric adverse reactions were similar to those seen in adult
patients.
Primary Generalized Tonic-Clonic Seizures
In the adjunctive therapy placebo-controlled trial for primary generalized tonic-clonic seizures, the
adverse reactions were generally similar to those that occurred in the partial-onset seizures trials.
The adverse reactions most commonly reported were dizziness, somnolence, headache, and
nausea.
VIMPAT is a Schedule V controlled substance.
MONOTHERAPY DOSING* FOR ADULT PATIENTS
A therapeutic dose (300 mg/day) may be achieved after one week.2
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Recommended maintenance dose
300 mg/day to 400 mg/day (150 mg-200 mg twice-daily). Titrate based on tolerability and response.
Conversion to monotherapy
- For adult patients who are already on a single AED and will convert to VIMPAT monotherapy, the therapeutic dose of 150 mg twice daily to 200 mg twice daily (300 mg/day to 400 mg/day) should be maintained for at least 3 days before initiating withdrawal of concomitant AED
- A gradual withdrawal of the concomitant AED over at least 6 weeks is recommended
Adverse reactions
In the adult monotherapy clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo-controlled trials for partial-onset seizures, with the exception of insomnia (occurred at a higher rate of ≥2%).
*monotherapy for partial-onset seizures only
ADJUNCTIVE THERAPY DOSING FOR ADULT PATIENTS
A therapeutic dose (200 mg/day) may be achieved after one week.2
(Tablets not shown at actual size.)
Recommended maintenance dose
200 mg/day to 400 mg/day (100 mg-200 mg twice-daily). Titrate based on tolerability and response.
Adverse reactions
In the adult placebo-controlled clinical trials for partial-onset seizures, the most frequently seen adverse reaction with VIMPAT was dizziness (31% vs 8% placebo). Other common adverse reactions occurring in ≥10 percent of VIMPAT-treated patients, and greater than placebo, were headache, nausea, and diplopia.
200 mg LOADING DOSE FOR ADULT PATIENTS
Use the VIMPAT loading dose when your adult patients need to get to a therapeutic dose more rapidly than standard titration allows. The use of a loading dose in pediatric patients has not been studied.
A single loading dose of 200 mg approximates steady-state concentrations comparable to the 100 mg twice-daily oral administration.
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Loading dose administration2
VIMPAT may be initiated in adult patients with a single loading dose of 200 mg (oral or injection) followed approximately 12 hours later by 100 mg twice-daily (200 mg/day).
- Based on individual response and tolerability, the dose can be increased at weekly intervals by 50 mg twice-daily (100 mg/day), as needed, up to the recommended monotherapy (300 mg/day to 400 mg/day) or adjunctive therapy (200 mg/day to 400 mg/day) maintenance dose
- The loading dose should be administered with medical supervision considering the VIMPAT pharmacokinetics and increased incidence of CNS adverse reactions
Adverse reactions
When administering a loading dose, the incidence of CNS adverse reactions, such as dizziness, somnolence, and paresthesia may be higher with 15-minute administration than over a 30- to 60-minute period.
INTRAVENOUS DOSING
Special considerations when using injection
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VIMPAT injection for intravenous use—indicated as short-term replacement when oral administration is not feasible.
- Intravenous injection can be administered in the same dosing regimens as oral dosing, including the loading dose. The dose may be infused over a period of 15 to 60 minutes
- Infusion over 30 to 60 minutes is preferable, and should be used when 15-minute administration is not required
- Intravenous infusion of VIMPAT may cause bradycardia, AV blocks, and ventricular tachyarrhythmia. Obtaining an ECG before beginning VIMPAT and after VIMPAT is titrated to steady-state maintenance dose is recommended in patients with underlying proarrhythmic conditions or on concomitant medications that affect cardiac conduction
- Cmax reached by end of infusion time
- Oral to intravenous (IV): the initial total daily IV dosage regimen of VIMPAT should be equivalent to the total daily dosage regimen of oral VIMPAT
- Adverse reactions with IV administration generally appeared similar to those observed with the oral formulation, although IV administration was associated with local adverse events, such as injection site pain or discomfort (2.5%), irritation (1%), and erythema (0.5%)
- Infusion durations less than 30 minutes are generally not recommended in pediatric patients
Intravenous injection solution preparation
- VIMPAT 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
- Product with particulate matter or discoloration should not be used
- VIMPAT injection is for single-dose only—any unused portion of VIMPAT injection should be discarded
ORAL SOLUTION DOSING
Special considerations when using oral solution
VIMPAT oral solution—a dosing option for patients who cannot swallow tablets2
- Does not need to be refrigerated or shaken prior to administration
- For accurate dosing, healthcare providers should offer a calibrated measuring device to patients prescribed VIMPAT oral solution
- Any unused oral solution should be discarded after 7 weeks of first opening the bottle
- IV to oral: begin oral administration at the equivalent daily dosage and frequency of the IV administration
- VIMPAT oral solution contains aspartame, a source of phenylalanine. A 200 mg dose of VIMPAT oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine
- Multiple bottle sizes (465 mL and 200 mL) provide convenient options for the pharmacy
SELECT IMPORTANT SAFETY INFORMATION
Risks in Patients with Phenylketonuria:
VIMPAT oral solution contains aspartame, a source of phenylalanine which can be harmful in patients with phenylketonuria (PKU). A 200 mg dose of VIMPAT oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine.
SELECT DOSING IN SPECIAL POPULATIONS FOR ADULT PATIENTS2
- Dosage adjustments are recommended for patients with mild or moderate hepatic impairment or severe renal impairment. Use in patients with severe hepatic impairment is not recommended. Dose titration should be performed with caution in all patients with renal and/or hepatic impairment
- Dose supplementation: Following a 4-hour hemodialysis treatment, a dose supplementation of up to 50% of the last dose administered should be considered
- Patients with hepatic or renal impairment taking strong inhibitors of CYP3A4 or CYP2C9 may have a significant increase in exposure to VIMPAT. Dose reduction may be necessary in these patients
- Caution should be exercised for dose titration in elderly patients
MULTIPLE FORMULATIONS AND A SIMPLE 1:1 DOSE CONVERSION FOR ADULT PATIENTS2
Tablets:
60-count bottles VIMPAT tablets should be swallowed whole with liquid. Do not divide VIMPAT tablets.
Injection solution
200 mg/20 mL:
single-use vial
Oral solution
10 mg/mL: 200 mL and
465 mL bottles
Unit-dose carton:
6 cards, 10 tablets each
(Formulations not shown at actual size.)
Convenient for the healthcare provider
- Available in dosage strengths of 50 mg, 100 mg, 150 mg, and 200 mg
- Multiple formulations
- IV formulation requires no diluent, reconstitution, or refrigeration
- Can be administered with or without common diluents
- Oral solution may also be administered using a nasogastric or gastrostomy tube
Blood levels
- No blood-level monitoring required
Pharmacokinetic profile
- Approximately 100% oral bioavailability
- VIMPAT injection is bioequivalent to oral VIMPAT when infused over 30 to 60 minutes*
- Linear pharmacokinetics
- Low protein binding (<15%)
Food and VIMPAT
- Can be given with or without food
- Food does not affect the rate or extent of absorption
For the 15-minute intravenous infusion, bioequivalence was met for AUC(0-tz) but not for Cmax. The point estimate of Cmax was 20% higher than Cmax for oral tablet and the 90% CI for Cmax exceeded the upper boundary of the bioequivalence range.
Reference
- 2.VIMPAT® (lacosamide): US prescribing information. Smyrna (GA): UCB, Inc.
