VIMPAT DOSING
VIMPAT DOSING
Monotherapy Dosing Adjunctive Therapy Dosing 200 mg Loading Dose IV and Oral Solution Dosing Select Dosing in Special Populations
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INDICATION
VIMPAT® is indicated in patients 17 years and older with partial-onset seizures as monotherapy or adjunctive therapy. VIMPAT injection for intravenous use is an alternative when oral administration is temporarily not feasible.
SELECT 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.
In the 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%). In adjunctive placebo-controlled trials, the most common adverse reactions (≥10% and greater than placebo) were dizziness, headache, nausea, and diplopia.
VIMPAT is a Schedule V controlled substance.
MONOTHERAPY DOSING
A therapeutic dose (300 mg/day) may be achieved after one week2
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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 patients who are already on 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 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 (occurred at a higher rate of ≥2%).
ADJUNCTIVE THERAPY DOSING
A therapeutic dose (200 mg/day) may be achieved after one week2
(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 placebo-controlled clinical trials, 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
Use the VIMPAT loading dose when your patients need to get to a therapeutic dose more rapidly than standard titration allows
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 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 feasible2
- 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
- Closely monitor patients with known cardiac conduction problems, on concomitant medications that prolong PR interval, or with severe cardiac disease, as intravenous infusion of VIMPAT may cause bradycardia or AV blocks in these patients
- 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%)
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
- 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 DOSING IN SPECIAL POPULATIONS2
- 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
- Following a 4-hour hemodialysis treatment, AUC of VIMPAT is reduced by approximately 50%, and dosage supplementation of up to 50% following hemodialysis 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
Tablets:
60-count bottles
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
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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
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
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.
Start with VIMPAT. Switch to VIMPAT. Add VIMPAT.
Reference
- 2.VIMPAT® (lacosamide): US prescribing information. Smyrna (GA): UCB, Inc., June 2015.
Important Safety Information
Warnings and Precautions
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including VIMPAT, increase the risk of suicidal behavior and ideation. Monitor patients taking VIMPAT for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients and caregivers to be alert for these behavioral changes and to immediately report them to the healthcare provider.
Dizziness and Ataxia
VIMPAT may cause dizziness and ataxia. The onset of dizziness and ataxia was most commonly observed during titration. Advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they are familiar with the effects of VIMPAT on their ability to perform such activities.
Cardiac Rhythm and Conduction Abnormalities
PR interval prolongation
Dose-dependent prolongations in PR interval with VIMPAT have been observed in clinical studies in patients and in healthy volunteers. Second-degree and complete AV block have been reported in patients in pain studies and in patients with seizures. When VIMPAT is given with other drugs that prolong the PR interval, further PR prolongation is possible.
Use VIMPAT with caution in patients with known cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block and sick sinus syndrome without pacemaker), sodium channelopathies (e.g., Brugada Syndrome), or with severe cardiac disease such as myocardial ischemia or heart failure, or structural heart disease. Also, use VIMPAT with caution in patients on concomitant medications that prolong PR interval (e.g., beta-blockers and calcium channel blockers) because of a risk of AV block or bradycardia. In such patients, obtaining an ECG before beginning VIMPAT, and after VIMPAT is titrated to steady-state, is recommended. In addition, closely monitor these patients if they are administered VIMPAT through the intravenous route.
Atrial fibrillation and Atrial flutter
VIMPAT administration may predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy and/or cardiovascular disease.
Syncope
VIMPAT may cause syncope.
Withdrawal of Antiepileptic Drugs
Gradually withdraw VIMPAT (over a minimum of 1 week) to minimize the potential of increased seizure frequency.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Also known as multi-organ hypersensitivity, has been reported with antiepileptic drugs. Some of these events have been fatal or life-threatening. If signs or symptoms are present, immediately evaluate the patient. Discontinue VIMPAT if an alternative etiology for the signs and symptoms cannot be established.
Phenylketonurics
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.
Adverse Reactions
Adjunctive therapy
In the placebo-controlled clinical trials, 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.
Monotherapy
In the clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo-controlled trials, with the exception of insomnia (occurred at a higher rate of ≥2%).
Injection
In adjunctive therapy clinical trials, adverse reactions with intravenous administration generally were similar to those that occurred with the oral formulation, although intravenous administration was associated with local adverse reactions such as injection site pain or discomfort (2.5%), irritation (1%), and erythema (0.5%). 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.
Dosing Considerations
The loading dose should be administered with medical supervision considering the VIMPAT pharmacokinetics and increased incidence of CNS adverse reactions. 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. Perform dose titration with caution in all patients with renal and/or hepatic impairment.
VIMPAT is a Schedule V controlled substance.
Please see full Prescribing Information.
For more information on VIMPAT® contact 844-599-CARE (2273).
INDICATION
VIMPAT® is indicated for the treatment of partial-onset seizures in patients 4 years of age and older. As the safety of VIMPAT injection in pediatric patients has not been established, VIMPAT injection is indicated for the treatment of partial-onset seizures only in adult patients (17 years of age and older).