Vimpat (lacosamide)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Lacosamide, a functionalized amino acid, is an anticonvulsant.
Lacosamide, a functionalized amino acid structurally related to serine, is an anticonvulsant. Although the precise mechanism(s) of its anticonvulsant action remains to be fully elucidated, available data suggest that lacosamide may have a dual mechanism of action, including modulation of the slow inactivation of sodium channels and modulation of collapsin response mediator protein-2 (CRMP-2)-mediated enurotropic signals. In vitro electrophysiologic studies have shown that lacosamide selectively enhances the slow inactivation of voltage-gated sodium channels without affecting fast inactivation.
This selective slow inactivation of sodium channels may result in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing. In addition, in preclinical testing, lacosamide was found to bind to CRMP-2, a phosphoprotein expressed mainly in the nervous system that is involved in neuronal differentiation, polarization, gene expression, and control of axonal outgrowth. However, in subsequent testing, such binding was not confirmed.
Lacosamide has demonstrated analgesic, antinociceptive, and anxiolytic activity in preclinical studies. The drug does not exhibit binding affinity for gamma-aminobutyric acid (GABA), N-methyl-d-aspartate (NMDA), adenosine, muscarinic, serotonin, histamine, dopamine, or other receptors. In addition, lacosamide does not affect the reuptake or metabolism of norepinephrine, dopamine, serotonin, or GABA.
The drug does not affect voltage-activated calcium channels (L-, N-, P/Q-, or T-type) or voltage-activated potassium channels and does not modulate delayed-rectifier or A-type potassium currents.
Lacosamide is rapidly and completely absorbed following oral administration. The oral bioavailability of lacosamide tablets is approximately 100%; food does not affect the rate and extent of absorption. Peak plasma concentrations of lacosamide occur approximately 0.5-4 hours following oral dosing and steady-state plasma concentrations are achieved after 3 days of twice-daily oral administration.
Following IV administration, peak plasma lacosamide concentrations are reached at the end of the infusion. When infused IV over 30 or 60 minutes, the IV formulation is bioequivalent to the oral tablets. The pharmacokinetics of both oral and IV lacosamide are dose-proportional over a dosage range of 100-800 mg and exhibit low intra- and intersubject variability.
Lacosamide is less than 15% bound to plasma proteins and has an elimination half-life of approximately 12-13 hours.
Lacosamide is primarily eliminated by renal excretion and biotransformation. Following oral and IV administration of a 100-mg radiolabeled dose of lacosamide, approximately 95% of the dose was recovered in the urine and less than 0.5% in the feces; the principal compounds excreted were unchanged lacosamide (approximately 40%), O-desmethyl-lacosamide (approximately 30%; inactive metabolite), and a structurally unknown polar fraction (approximately 20%; possibly serine derivatives). Lacosamide is a substrate of the cytochrome P-450 (CYP) isoenzyme 2C19; the relative contribution of other CYP isoenzymes or non-CYP enzymes in the metabolism of the drug is unclear.
No clinically relevant differences in the pharmacokinetics of lacosamide were observed between poor and extensive metabolizers of CYP2C19 substrates; however, plasma concentrations and the amount excreted in the urine of the O-desmethyl metabolite were reduced by about 70% in poor metabolizers compared with extensive metabolizers.
USES: Lacosamide is used to treat seizures.
Generic name: lacosamide
Pronunciation: (la-KOE-sa-mide)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Vimpat
Indications
The following indications are listed for Vimpat:
- Focal Epilepsy
- Partial Epilepsy Treatment Adjunct
- Tonic-Clonic Epilepsy Treatment Adjunct
Also known as: Cortical Epilepsy, Focal Seizures, Grand Mal Epilepsy Treatment Adjunct, Local Epilepsy, Partial Epilepsy, Partial Onset Seizures, Partial Onset Seizures Treatment Adjunct, Partial Seizures, Partial Seizures Treatment Adjunct, Tonic-Clonic Seizures Treatment Adjunct.
Dosing
No dosing information is available for this tab.
Lacosamide is administered orally (as tablets or oral solution). The drug may be administered by IV infusion in adults when oral administration is temporarily not feasible (e.g., after surgery or in patients with dysphagia or acute GI disorders); safety of the IV formulation has not been established in pediatric patients.
Bioequivalence has been demonstrated between the oral tablets and the 30- and 60-minute IV infusions (but not the 15-minute IV infusion) of lacosamide. The commercially available oral solution containing 50 mg/5 mL of lacosamide is bioequivalent to the tablets.
Cardiac conduction abnormalities and arrhythmias have been observed in patients receiving lacosamide orally or by IV infusion; the manufacturer recommends ECG monitoring prior to initiating therapy and after reaching steady-state maintenance dosage in patients who may be at risk. In addition, the manufacturer recommends close monitoring in patients receiving lacosamide by IV infusion. (See Cardiac Effects under Cautions: Warnings/Precautions.)
Lacosamide therapy should be withdrawn gradually (e.g., by discontinuing therapy over at least one week) to minimize the potential for increased seizure frequency in patients with seizure disorders.
Patients currently receiving or beginning therapy with lacosamide and/or any other anticonvulsant for any indication should be closely monitored for the emergence or worsening of depression, suicidal thoughts or behavior (suicidality), and/or any unusual changes in mood or behavior. (See Suicidality Risk under Cautions: Warnings/Precautions.)
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Lacosamide generally appears to have a low potential for pharmacokinetic drug interactions with other anticonvulsants or other drugs.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
The manufacturer states that there are no known contraindications to the use of lacosamide.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse reactions occurring in 5% or more of patients receiving oral lacosamide as adjunctive therapy in controlled clinical trials for partial-onset seizures and reported more frequently than with placebo include dizziness, headache, diplopia, nausea, vomiting, fatigue, blurred vision, ataxia, somnolence, tremor, nystagmus, memory impairment, balance disorder, vertigo, and diarrhea.
Adverse effects reported in the study evaluating lacosamide monotherapy generally were similar to those reported in the adjunctive placebo-controlled studies with the exception of insomnia (occurring in 2% or more of patients receiving lacosamide monotherapy).
Systemic adverse effects associated with short-term IV lacosamide therapy in patients with partial-onset seizures generally appear to be consistent with those associated with oral administration of the drug; local adverse effects include injection site pain or discomfort, irritation, and erythema.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of lacosamide in pediatric patients younger than 4 years of age have not been established. Use of lacosamide tablets and oral solution in pediatric patients 4 years of age and older is supported by data from partial-onset seizure studies in adults, pharmacokinetic studies in adults and pediatric patients, and safety data in pediatric patients. Safety of lacosamide injection has not been established in pediatric patients.
Lacosamide has been shown in vitro to interfere with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth; potential adverse effects on CNS development cannot be ruled out. (See Description.) Administration of lacosamide to rats during the neonatal and juvenile periods of postnatal development resulted in decreased brain weights and long-term neurobehavioral changes (e.g., altered open field performance, deficits in learning and memory). The no-effect dosage for developmental neurotoxicity in rats was associated with an area under the plasma concentration-time curve (AUC) less than that in humans at the maximum recommended dosage of 400 mg daily.
There are no adequate data in humans to determine if there is any risk associated with the use of lacosamide during pregnancy. In animal studies, lacosamide produced developmental toxicity (i.e., increased embryofetal and perinatal mortality, growth deficit) when given orally to pregnant rats. Developmental neurotoxicity was observed in animals given lacosamide during a period of postnatal development corresponding to the third trimester of human pregnancy. These effects were observed at dosages associated with clinically relevant plasma exposures.
Women who are pregnant while receiving lacosamide should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry; patients can enroll by calling 888-233-2334. Information on the registry also can be found on the website https://www.aedpregnancyregistry.org.
Lacosamide and/or its metabolites are distributed into milk of lactating rats. It is not known if lacosamide is distributed into human milk. The effects of lacosamide on the nursing infant or on milk production also are not known. The known benefits of breast-feeding should be considered along with the mother's clinical need for lacosamide and any potential adverse effects on the infant from the drug or underlying maternal condition.
Clinical studies of lacosamide did not include sufficient numbers of geriatric patients to determine whether they respond differently than younger patients. Systemic exposure and peak plasma concentrations of lacosamide (normalized for dosage and body weight) were approximately 20% higher in geriatric individuals compared with younger individuals, which may be related to differences in body weight and renal clearance. (See Dosage and Administration: Special Populations.)
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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