Lacosamide is a functionalized amino acid antiepileptic indicated for the treatment of partial onset and primary generalized tonic-clonic seizures. Psychological dependence may be possible as euphoria-type reactions similar to the alprazolam have been reported and a high rate of euphoria was reported compared to placebo during premarketing evaluation of the drug. Both oral and intravenous dosage forms are available; the injectable form can be used when oral administration is temporarily not feasible. The clinical study experience of intravenous lacosamide is limited to 5 days of consecutive treatment.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Administer loading doses with medical supervision due to possible increased risk of central nervous system or cardiovascular adverse reactions.
Route-Specific Administration
Oral Administration
-May be administered without regard to meals.
Oral Solid Formulations
-Immediate-release tablets: Swallow tablets whole with liquid. Do not divide the tablets.
-Extended-release capsules: Swallow capsules whole with liquid. Do not open, chew, or crush the capsules.
Oral Liquid Formulations
-Measure dosage with an oral syringe or calibrated measuring device.
-May administer through a nasogastric or gastrostomy tube.
-Storage: Do not freeze. Discard any unused solution remaining after 6 months of first opening the bottle.
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Intermittent IV Infusion
-Administer undiluted or mixed with 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer's Injection.
-Infuse over 30 to 60 minutes (recommended). Infusions as rapid as 15 minutes can be administered in adults if needed.
-Storage: Diluted solution can be stored for up to 4 hours at room temperature.
Intermittent IV Push*
NOTE: Lacosamide is not FDA-approved for administration via IV push.
-Undiluted lacosamide has been administered IV in doses of up to 400 mg and at a rate of 40 to 80 mg/minute to patients in status epilepticus.
-In a retrospective study of 48 patients (age: 17 to 95 years) in status epileptics, a median bolus dose of 200 mg (range 200 to 400 mg) was administered undiluted at a rate of 60 mg/minute. Two patients reported skin rash and pruritus.
-In a retrospective study of 39 patients (age: 18 to 90 years) in status epilepticus, a median bolus dose of 400 mg (range 200 to 400 mg) was administered undiluted at a rate of 40 to 80 mg/minute. Adverse reactions reported were mild and thought to be due to other medications such as benzodiazepines or propofol (hypotension, sedation, and 1 allergic skin reaction).
-A retrospective cohort study in patients (age: 49 to 69 years) receiving intravenous lacosamide (indication not specified) compared diluted lacosamide infused over 30 minutes (n = 88) to undiluted IV push lacosamide given at a rate of 80 mg/minute (n = 78). Hypotension (8% vs. 10.3%) and bradycardia (2.3% vs. 2.6%) were similar between the 2 groups; no infusion reactions occurred.
Dizziness (16% to 53% vs. 7% to 8%), ataxia (4% to 15% vs. 2%), vertigo (3% to 5% vs. 1%), fatigue (7% to 15% vs. 6%), gait disturbance (4% or less vs. less than 1%), asthenia (2% to 4% vs. 1%), headache (11% to 14% vs. 9% to 10%), drowsiness (5% to 17% vs. 5% to 14%), tremor (4% to 12% vs. 4%), balance disorder (1% to 6% vs. 0%), nystagmus (2% to 10% vs. 4%), and memory impairment (1% to 6% vs. 2%) were reported during placebo-controlled clinical trials of lacosamide. Vertigo, dizziness, and ataxia led to discontinuation in more than 1% of patients and more frequently with lacosamide than placebo. Dizziness and ataxia were also observed in pediatric clinical trials. Dizziness and ataxia are more likely to occur during dose titration or when doses more than 400 mg/day are used. If a loading dose is clinically indicated, administer with medical supervision because of the possibility of increased incidence of CNS adverse reactions such as dizziness and ataxia. Myoclonic epilepsy was reported in 3% of lacosamide-treated patients compared to 1% of those receiving placebo during trials for generalized tonic-clonic seizures. Additionally, 2 patients had acute worsening of seizures shortly after drug initiation, 1 of these patients progressed to status epilepticus. Paresthesias, cognitive disorder, hypoesthesia, dysarthria, disturbance in attention, feeling drunk, falls, and acute cerebellar syndrome were reported during controlled clinical trials and open-label extension studies. Insomnia, dyskinesia, and new or worsening seizures have been reported during postmarketing use of lacosamide.
Psychiatric adverse reactions that occurred during placebo-controlled clinical trials in at least 2% of patients receiving 200 to 600 mg/day of lacosamide and more frequently than in those receiving placebo included confusion (2% to 4% vs. 3%) and depression (2% vs. 1%). Irritability, confusional state, depressed mood, and altered mood were reported during controlled clinical trials and open-label extension studies in patients with partial seizures. During postmarketing use, aggression, agitation, hallucinations, and psychosis (psychotic disorder) have been reported. Anticonvulsants are thought to carry an increased risk of suicidal ideation and behavior. An analysis of previously gathered drug data showed that patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation (0.43%) as patients receiving placebo (0.24%). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions. Age was not a determining factor. The increased risk of suicidal ideation and behavior occurred between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. All patients beginning treatment with lacosamide or currently receiving such treatment should be closely monitored for altered mood, emerging or worsening suicidal thoughts/behavior, or depression. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior.
Nausea (7% to 17% vs. 4% to 6%), vomiting (6% to 16% vs. 3%), and diarrhea (3% to 5% vs. 3%) were reported in placebo-controlled trials of lacosamide. Nausea and vomiting lead to discontinuation in more than 1% of patients and more frequently with lacosamide than placebo. Other GI effects including constipation, dyspepsia, xerostomia, and oral hypoesthesia were reported during controlled clinical trials and open-label extension studies in patients with partial seizures, although the frequencies are unknown and causality to the drug has not been established.
Ophthalmic effects that occurred during clinical trials in at least 2% of patients receiving 200 to 600 mg/day of lacosamide and with an incidence more than placebo included diplopia (6% to 16% vs. 2%), and blurred vision (2% to 16% vs. 3%). These adverse reactions lead to discontinuation in more than 1% of patients and more frequently with lacosamide than placebo.
Dose-dependent PR prolongation with lacosamide has been observed in clinical studies in adults and in healthy volunteers. Electrocardiographic effects of lacosamide were determined in a double-blind, randomized trial in healthy subjects (n = 247). Chronic oral doses of lacosamide 400 and 800 mg/day (equal to and 2 times the maximum daily recommended dose, respectively) were compared with placebo and a positive control (moxifloxacin 400 mg). At steady-state, the time of the maximum observed mean PR interval corresponded with Tmax. The placebo-subtracted maximum increase in PR interval (at Tmax) was 7.3 milliseconds for the 400 mg/day group and 11.9 milliseconds for the 800 mg/day group. For patients who participated in the controlled trials, the placebo-subtracted mean maximum increase in PR interval for lacosamide 400 mg/day was 3.1 milliseconds in patients with partial-onset seizures and 9.4 milliseconds for patients with diabetic neuropathy. In adjunctive clinical trials in adults with partial-onset seizures, asymptomatic first-degree AV block was observed in 0.4% (4/944) of patients randomized to receive lacosamide and 0% (0/364) of patients randomized to receive placebo. A case of profound bradycardia (i.e., 26 bpm) occurred in a patient, who was also receiving a beta-blocker, during a 15-minute infusion of lacosamide 150 mg; the infusion was discontinued and the patient experienced a rapid recovery. When lacosamide is given with other drugs that prolong the PR interval, further PR prolongation is possible. In the postmarketing setting, there have been reports of cardiac arrhythmias in patients treated with lacosamide, including bradycardia, AV block, and ventricular tachycardia, which have rarely resulted in asystole, cardiac arrest, and death. Most cases have occurred in patients with underlying proarrhythmic conditions, or in those taking concomitant medications that affect cardiac conduction or prolong the PR interval. These events have occurred with both oral and intravenous routes of administration and at prescribed doses as well as in the setting of overdose. If a loading dose is clinically indicated, administer the loading dose with medical supervision because of the possibility of increased incidence of cardiovascular adverse reactions. Both atrial fibrillation and atrial flutter have been reported in open-label partial-onset seizure trials and in postmarketing experience. In adults with diabetic neuropathy, for which lacosamide is not indicated, 0.5% of patients treated with lacosamide experienced atrial fibrillation or atrial flutter and 1.2% of patients treated with lacosamide experienced syncope or loss of consciousness compared to 0% of patients given placebo. Most of the cases of syncope were observed in patients receiving doses above 400 mg/day. The cause of syncope was not determined in most cases. However, several were associated with either orthostatic hypotension, atrial flutter/fibrillation (and associated tachycardia), or bradycardia. Cases of syncope have also been observed in open-label clinical partial-onset seizure studies in adult and pediatric patients. These cases were associated with a history of risk factors for cardiac disease and the use of drugs that slow AV conduction. Palpitations have been reported during postmarketing experience with lacosamide.
Reactions associated with IV administration of lacosamide have included injection site reaction (e.g., pain or discomfort (2.5%), irritation (1%), and erythema (0.5%)). Bradycardia (i.e., 26 bpm) occurred in 1 patient during an infusion of lacosamide; the patient was also receiving a beta-blocker and the bradycardia was reversible upon discontinuation of lacosamide.
Dermatologic effects that occurred during clinical trials in at least 2% of patients receiving 200 to 600 mg/day of lacosamide and with an incidence more than placebo included skin laceration (2% to 3% vs. 2%) and pruritus (2% to 3% vs. 1%). Angioedema, rash, and urticaria have been reported during postmarketing use. In a retrospective cohort study (n = 686), the incidence of rash within 30 days of discontinuation of intravenous lacosamide was 2-fold higher in pediatric patients who were treated with the alternate initial dosage regimen to achieve the maintenance dosage in a shorter timeframe compared to patients who were treated with a lower initial dosage regimen.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking lacosamide. DRESS typically 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. Eosinophilia is often present. Evaluate the patient immediately if signs or symptoms of hypersensitivity (e.g., fever, lymphadenopathy, rash) are present. Discontinue lacosamide if an alternative etiology cannot be established. A single case of hepatitis with elevated hepatic enzymes more than 20 times the upper limit of normal (ULN) and nephritis (proteinuria and urine casts) consistent with a delayed multiorgan hypersensitivity reaction was observed 10 days after lacosamide treatment completion. Transaminases returned to normal within 1 month without specific treatment. Elevations of alanine aminotransferase (ALT) to 3 times the ULN or more occurred in 0.7% of study patients with partial seizures receiving adjunct lacosamide (in combination with 1 to 3 other anticonvulsants) vs. 0% of patients receiving placebo.
Neutropenia and anemia were reported during controlled clinical trials and open-label extension studies in patients with partial seizures, although the frequencies are unknown and causality to lacosamide has not been established. Also, agranulocytosis has been reported during postmarketing use of lacosamide.
Tinnitus was reported during controlled clinical trials and open-label extension studies in patients with partial seizures, although the frequency is unknown and causality to lacosamide has not been established.
Muscle spasms (e.g., muscle cramps) were reported during controlled clinical trials and open-label extension studies in patients with partial seizures, although the frequency is unknown and causality to lacosamide has not been established.
Abrupt discontinuation of lacosamide in patients with diabetic neuropathy did not produce signs or symptoms indicative of physical dependence during clinical trials. However, psychological dependence may be possible based upon reports of euphoria-type reactions that are indistinguishable from the benzodiazepine alprazolam at a lacosamide dose of 800 mg. During a single-dose study assessing human abuse potential (n = 34), dose-related euphoria occurred in significantly more patients who received 200 and 800 mg of lacosamide compared to placebo; 15% of those who received 800 mg of lacosamide reported euphoria compared to none in the placebo group. During 2 pharmacokinetic studies, lacosamide doses of 300 to 800 mg were associated with a 6% to 25% incidence of euphoria compared to 0% in the placebo group. It should be noted that the rate of euphoria reported in the development program was less than 1%.
Lacosamide is contraindicated in patients who have demonstrated a hypersensitivity to the drug or its ingredients. Once case of symptomatic hepatitis and nephritis consistent with a delayed multiorgan hypersensitivity reaction (i.e., Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)) was observed during clinical trials. If a multiorgan hypersensitivity reaction is suspected, lacosamide should be discontinued. Patients should be instructed to promptly report potential signs of multiorgan hypersensitivity reactions, such as fever or rash, to their health care provider.
Monitor all patients beginning treatment with antiepileptic drugs (AEDs) or currently receiving lacosamide closely for emerging or worsening depression or suicidal ideation. Advise patients and caregivers of the increased risk of suicidal thoughts and behaviors and to immediately report the emergence of new or worsening of depression, suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. AEDs should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with an increased risk of suicidal thoughts and behavior. If suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any patient may be related to the illness being treated. There is an increased risk of suicidal ideation and behavior in patients receiving AEDs to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). The primary analysis consisted of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (5 years of age and older). There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving AEDs had approximately twice the risk of suicidal behavior or ideation as patients receiving placebo (0.43% vs. 0.24%, respectively; RR 1.8, 95% CI: 1.2 to 2.7). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions; however, the absolute risk differences were similar in trials for epilepsy and psychiatric indications. Age was not a determining factor. The increased risk of suicidal ideation and behavior was observed between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks.
Use lacosamide with caution in patients with underlying proarrhythmic conditions such as cardiac conduction abnormalities (e.g., first-degree AV block, second-degree or higher AV block, sick sinus syndrome without pacemaker, sodium channelopathies like Brugada syndrome, or on concomitant medications that prolong the PR interval), severe cardiac disease (e.g., myocardial ischemia, history of myocardial infarction, recent acute myocardial infarction, heart failure, structural heart disease), and bradycardia. In such patients, obtain an ECG prior to treatment initiation and after lacosamide is titrated to the maintenance dose. In addition, closely monitor these patients if lacosamide is administered through the intravenous route. If a loading dose is clinically indicated, administer the loading dose with medical supervision because of the possibility of increased incidence of cardiovascular adverse reactions. Dose-dependent prolongation of the PR interval with lacosamide has been observed in clinical studies in adults and in healthy volunteers. In the postmarketing setting, there have been reports of cardiac arrhythmias in patients treated with lacosamide, which have rarely resulted in asystole, cardiac arrest, and death.
Lacosamide may predispose patients, especially those with diabetic neuropathy and/or cardiovascular disease, to atrial arrhythmias (atrial fibrillation or atrial flutter) and syncope. Most episodes of syncope were associated with high dose therapy (doses more than 400 mg/day); however, several cases were associated with either changes in orthostatic blood pressure, atrial fibrillation, atrial flutter, or bradycardia. Instruct patients on preventative measures for orthostatic hypotension, such as rising slowly from a seated position. Use lacosamide cautiously in patients with cardiac disease or other conditions that may predispose patients to hypotension (e.g., dehydration, hypovolemia).
Psychological dependence may be possible based upon reports of euphoria-type reactions occurring in patients receiving lacosamide, including clinical trial data from pharmacokinetic and human abuse potential studies. Lacosamide should be used in patients with a history of substance abuse only if the benefit justifies the potential risk of dependence.
Avoid abrupt discontinuation of lacosamide. Withdraw lacosamide gradually (i.e., over a minimum of 1 week) to minimize the potential for increased seizure frequency.
Lacosamide may cause dizziness, double vision, abnormal coordination and balance, and somnolence. Advise patients receiving lacosamide to avoid driving or operating machinery, or engaging in other hazardous activities until they have become accustomed to any such effects associated with lacosamide. If a loading dose is clinically indicated, administer with medical supervision because of the possibility of increased incidence of CNS adverse reactions.
Careful dose titration is recommended for patients with renal impairment. The AUC of lacosamide is increased 25% in those with mild to moderate renal impairment and 60% in those with severe renal impairment. Dosage adjustments are recommended in patients with severe renal impairment or endstage renal disease (e.g., renal failure). Use caution in patients with mild to moderate renal disease. Due to removal of lacosamide by dialysis, dosage supplementation should be considered.
Careful dose titration is recommended for patients with hepatic disease since lacosamide is partially metabolized via the liver. The AUC of lacosamide is increased 50 to 60% in patients with moderate hepatic impairment compared to healthy subjects; therefore, dosage adjustments are recommended in patients with mild to moderate hepatic impairment. Lacosamide is not recommended for use in patients with severe hepatic impairment since the drug has not been studied in this patient population.
Before using lacosamide oral solution in a person with phenylketonuria, consider the combined daily amount of phenylalanine from all sources, including lacosamide oral solution, which contains aspartame, a source of phenylalanine. A 200 mg dose of lacosamide oral solution contains 0.32 mg of phenylalanine.
There were insufficient numbers of geriatric patients (n = 18) enrolled in partial-onset seizure trials to adequately assess the effectiveness of lacosamide in this population. The AUC and Cmax of lacosamide are approximately 20% higher in geriatric compared to younger adults after normalization for body weight. The slightly higher lacosamide plasma concentrations in elderly subjects are possibly caused by differences in total body water (lean body weight) and age-associated decreased renal clearance; no dose adjustment based on age alone is considered necessary. Dose adjustments for severe renal impairment (CrCl less than 30 mL/min) are recommended in any age group. Careful dose titration is advisable in the elderly. According to the Beers Criteria, anticonvulsants are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, except for treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If lacosamide must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities; the use of any anticonvulsant for any condition should be based on confirmation of the condition and its potential cause(s). Determine effectiveness and tolerability by evaluating symptoms, and use these as the basis for dosage adjustment for most patients. Therapeutic drug monitoring is not required or available for most anticonvulsants. Serum medication concentrations (when available) may assist in identifying toxicity. Monitor the treated patient for drug efficacy and side effects. Anticonvulsants can cause a variety of side effects; some adverse reactions can increase the risk of falls. When an anticonvulsant is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity as outlined in the OBRA guidelines.
Data with lacosamide in pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Results from animal studies suggest that various fetal developmental toxicities are possible (e.g., increased embryofetal and perinatal mortality, growth deficit, developmental neurotoxicity). In addition, decreased brain weights and long-term neurobehavioral changes (i.e., altered open field performance, deficits in learning and memory) occurred in neonatal and juvenile rats receiving oral lacosamide. The early postnatal period in rats is thought to correspond to the brain development that occurs in late pregnancy in humans. In vitro data indicate that lacosamide interferes with the activity of collapsin response mediator protein-2, which is involved in neuronal differentiation and control of axonal growth. No adverse effects on male or female fertility or reproduction have been observed during animal studies. The effect of lacosamide on labor and delivery in humans is not known; there was a tendency toward prolonged gestation in lacosamide-treated rats in animal studies. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to lacosamide; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.
Lacosamide is present in human milk. Monitor infants exposed to lacosamide during breast-feeding for excess sedation. Increased sleepiness has been reported in infants exposed to lacosamide through breast milk. The effects of lacosamide on milk production are unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for lacosamide and any potential adverse effects on the breast-fed infant from lacosamide or the underlying maternal condition.
General dosing information
-For persons converting to lacosamide monotherapy from another single anticonvulsant, do not withdraw the concomitant anticonvulsant until the therapeutic dose of lacosamide has been maintained for at least 3 to 4 days. A gradual withdrawal of the concomitant anticonvulsant over at least 6 weeks is recommended.
For the treatment of partial seizures:
-for the treatment of partial seizures as monotherapy:
Oral dosage (immediate-release):
Adults : 100 mg PO twice daily or alternatively, 200 mg PO as a single dose, then 100 mg PO twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 150 to 200 mg PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Adolescents 17 years: 100 mg PO twice daily or alternatively, 200 mg PO as a single dose, then 100 mg PO twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 150 to 200 mg PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Children and Adolescents 1 to 16 years weighing 50 kg or more: 50 mg PO twice daily or alternatively, 200 mg PO as a single dose, then 100 mg PO twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 150 to 200 mg PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Children and Adolescents 1 to 16 years weighing 30 to 49 kg: 1 mg/kg/dose PO twice daily or alternatively, 4 mg/kg/dose PO as a single dose, then 2 mg/kg/dose PO twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 2 to 4 mg/kg/dose PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Infants, Children, and Adolescents 1 month to 16 years weighing 6 to 29 kg: 1 mg/kg/dose PO twice daily or alternatively, 4.5 mg/kg/dose PO as a single dose, then 3 mg/kg/dose PO twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 3 to 6 mg/kg/dose PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Infants weighing less than 6 kg: 1 mg/kg/dose PO twice daily or alternatively, 3.75 mg/kg/dose PO twice daily, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 3.75 to 7.5 mg/kg/dose PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Oral dosage (extended-release):
Adults: 200 mg PO once daily, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 300 mg to 400 mg PO once daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Adolescents 17 years: 200 mg PO once daily, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 300 mg to 400 mg PO once daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Children and Adolescents 1 to 16 years weighing 50 kg or more: 100 mg PO once daily, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 300 mg to 400 mg PO once daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Intravenous dosage:
Adults : 100 mg IV twice daily or alternatively, 200 mg IV as a single dose, then 100 mg IV twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 150 to 200 mg IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Adolescents 17 years: 100 mg IV twice daily or alternatively, 200 mg IV as a single dose, then 100 mg IV twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 150 to 200 mg IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Children and Adolescents 1 to 16 years weighing 50 kg or more: 50 mg IV twice daily or alternatively, 200 mg IV as a single dose, then 100 mg IV twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 150 to 200 mg IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Children and Adolescents 1 to 16 years weighing 30 to 49 kg: 1 mg/kg/dose IV twice daily or alternatively, 4 mg/kg/dose IV as a single dose, then 2 mg/kg/dose IV twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 2 to 4 mg/kg/dose IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Infants, Children, and Adolescents 1 month to 16 years weighing 6 to 29 kg: 1 mg/kg/dose IV twice daily or alternatively, 4.5 mg/kg/dose IV as a single dose, then 3 mg/kg/dose IV twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 3 to 6 mg/kg/dose IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Infants weighing less than 6 kg: 0.66 mg/kg/dose IV 3 times daily or alternatively, 2.5 mg/kg/dose IV 3 times daily, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 2.5 to 5 mg/kg/dose IV 3 times daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
-for the treatment of partial seizures as an adjunct:
Oral dosage (immediate-release):
Adults : 50 mg PO twice daily or alternatively, 200 mg PO as a single dose, then 100 mg PO twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Adolescents 17 years: 50 mg PO twice daily or alternatively, 200 mg PO as a single dose, then 100 mg PO twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Children and Adolescents 1 to 16 years weighing 50 kg or more: 50 mg PO twice daily or alternatively, 200 mg PO as a single dose, then 100 mg PO twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Children and Adolescents 1 to 16 years weighing 30 to 49 kg: 1 mg/kg/dose PO twice daily or alternatively, 4 mg/kg/dose PO as a single dose, then 2 mg/kg/dose PO twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 2 to 4 mg/kg/dose PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Infants, Children, and Adolescents 1 month to 16 years weighing 6 to 29 kg: 1 mg/kg/dose PO twice daily or alternatively, 4.5 mg/kg/dose PO as a single dose, then 3 mg/kg/dose PO twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 3 to 6 mg/kg/dose PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Infants weighing less than 6 kg: 1 mg/kg/dose PO twice daily or alternatively, 3.75 mg/kg/dose PO twice daily, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 3.75 to 7.5 mg/kg/dose PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Oral dosage (extended-release):
Adults: 100 mg PO once daily, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 200 to 400 mg PO once daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Adolescents 17 years: 100 mg PO once daily, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 200 to 400 mg PO once daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Children and Adolescents 1 to 16 years weighing 50 mg or more: 100 mg PO once daily, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 200 mg to 400 mg PO once daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Intravenous dosage:
Adults : 50 mg IV twice daily or alternatively, 200 mg IV as a single dose, then 100 mg IV twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Adolescents 17 years: 50 mg IV twice daily or alternatively, 200 mg IV as a single dose, then 100 mg IV twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Children and Adolescents 1 to 16 years weighing 50 kg or more: 50 mg IV twice daily or alternatively, 200 mg IV as a single dose, then 100 mg IV twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Children and Adolescents 1 to 16 years weighing 30 to 49 kg: 1 mg/kg/dose IV twice daily or alternatively, 4 mg/kg/dose IV as a single dose, then 2 mg/kg/dose IV twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 2 to 4 mg/kg/dose IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Infants, Children, and Adolescents 1 month to 16 years weighing 6 to 29 kg: 1 mg/kg/dose IV twice daily or alternatively, 4.5 mg/kg/dose IV as a single dose, then 3 mg/kg/dose IV twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 3 to 6 mg/kg/dose IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Infants weighing less than 6 kg: 0.66 mg/kg/dose IV 3 times daily or alternatively, 2.5 mg/kg/dose IV 3 times daily, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 2.5 to 5 mg/kg/dose IV 3 times daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
For the treatment of generalized tonic-clonic seizures as an adjunct:
Oral dosage (immediate-release):
Adults: 50 mg PO twice daily or alternatively, 200 mg PO as a single dose, then 100 mg PO twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Adolescents 17 years: 50 mg PO twice daily or alternatively, 200 mg PO as a single dose, then 100 mg PO twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Children and Adolescents 4 to 16 years weighing 50 kg or more: 50 mg PO twice daily or alternatively, 200 mg PO as a single dose, then 100 mg PO twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Children and Adolescents 4 to 16 years weighing 30 to 49 kg: 1 mg/kg/dose PO twice daily or alternatively, 4 mg/kg/dose PO as a single dose, then 2 mg/kg/dose PO twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 2 to 4 mg/kg/dose PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Children and Adolescents 4 to 16 years weighing 11 to 29 kg: 1 mg/kg/dose PO twice daily or alternatively, 4.5 mg/kg/dose PO as a single dose, then 3 mg/kg/dose PO twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 3 to 6 mg/kg/dose PO twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended.
Intravenous dosage:
Adults: 50 mg IV twice daily or alternatively, 200 mg IV as a single dose, then 100 mg IV twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Adolescents 17 years: 50 mg IV twice daily or alternatively, 200 mg IV as a single dose, then 100 mg IV twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Children and Adolescents 4 to 16 years weighing 50 kg or more: 50 mg IV twice daily or alternatively, 200 mg IV as a single dose, then 100 mg IV twice daily starting 12 hours later, initially. May increase the dose by 100 mg/day at weekly intervals based on response and tolerability. Usual dose: 100 to 200 mg IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Children and Adolescents 4 to 16 years weighing 30 to 49 kg: 1 mg/kg/dose IV twice daily or alternatively, 4 mg/kg/dose IV as a single dose, then 2 mg/kg/dose IV twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 2 to 4 mg/kg/dose IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Children and Adolescents 4 to 16 years weighing 11 to 29 kg: 1 mg/kg/dose IV twice daily or alternatively, 4.5 mg/kg/dose IV as a single dose, then 3 mg/kg/dose IV twice daily starting 12 hours later, initially. May increase the dose by 2 mg/kg/day at weekly intervals based on response and tolerability. Usual dose: 3 to 6 mg/kg/dose IV twice daily. When discontinuing therapy, a gradual withdrawal over at least 1 week is recommended. Clinical study experience is limited to 5 consecutive days of IV therapy.
Maximum Dosage Limits:
-Adults
400 mg/day PO or IV.
-Geriatric
400 mg/day PO or IV.
-Adolescents
17 years: 400 mg/day PO or IV.
13 to 16 years weighing 50 kg or more: 400 mg/day PO or IV.
13 to 16 years weighing 30 to 49 kg: 8 mg/kg/day PO or IV. Safety and efficacy of the extended-release capsules have not been established.
13 to 16 years weighing 11 to 29 kg: 12 mg/kg/day PO or IV. Safety and efficacy of the extended-release capsules have not been established.
-Children
weighing 50 kg or more: 400 mg/day PO or IV.
weighing 30 to 49 kg: 8 mg/kg/day PO or IV. Safety and efficacy of the extended-release capsules have not been established.
weighing 6 to 29 kg: 12 mg/kg/day PO or IV. Safety and efficacy of the extended-release capsules have not been established.
-Infants
Safety and efficacy of the extended-release capsules have not been established.
weighing 6 to 29 kg: 12 mg/kg/day PO or IV.
weighing less than 6 kg: 15 mg/kg/day PO or IV.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
A reduction of 25% of the maximum dosage is recommended for persons with mild to moderate hepatic impairment; use caution during dose titration. Lacosamide use is not recommended in persons with severe hepatic impairment. Additionally, persons with hepatic impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 may have a significant increase in exposure to lacosamide; dosage reduction may be necessary.
Patients with Renal Impairment Dosing
CrCl 30 mL/minute or more (adults) or CrCl 30 mL/minute/1.73m2 or more (pediatrics): No dosage adjustments are needed; use caution during dose titration. Persons with renal impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 may have a significant increase in exposure to lacosamide; dosage reduction may be necessary.
CrCl less than 30 mL/minute (adults) or CrCl less than 30 mL/minute/1.73m2 (pediatrics) or end-stage renal disease: A reduction of 25% of the maximum dosage is recommended; use caution during dose titration. Persons with renal impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 may have a significant increase in exposure to lacosamide; additional dosage reduction may be necessary.
Intermittent hemodialysis
Lacosamide is removed by hemodialysis. After a 4-hour hemodialysis treatment, consider a supplemental dose of up to 50%.
*non-FDA-approved indication
Acebutolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Alprazolam: (Moderate) Concomitant administration of alprazolam with CNS-depressant drugs, including anticonvulsants, can potentiate the CNS effects of either agent.
Amiodarone: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class III antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Amlodipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Amlodipine; Atorvastatin: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Amlodipine; Benazepril: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Amlodipine; Celecoxib: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Amlodipine; Olmesartan: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Amlodipine; Valsartan: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Atazanavir: (Moderate) Lacosamide causes PR interval prolongation in some patients. Caution is advised during coadministration of lacosamide with other drugs that cause PR prolongation, such as atazanavir, since further PR prolongation is possible. If concurrent use is necessary, an ECG is recommended prior to initiation of lacosamide and after the drug is titrated to the maintenence dose. Patients receiving intravenous lacosamide should be closely monitored due to the potential for profound bradycardia and AV block during coadministration.
Atazanavir; Cobicistat: (Moderate) Lacosamide causes PR interval prolongation in some patients. Caution is advised during coadministration of lacosamide with other drugs that cause PR prolongation, such as atazanavir, since further PR prolongation is possible. If concurrent use is necessary, an ECG is recommended prior to initiation of lacosamide and after the drug is titrated to the maintenence dose. Patients receiving intravenous lacosamide should be closely monitored due to the potential for profound bradycardia and AV block during coadministration.
Atenolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Atenolol; Chlorthalidone: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Beta-adrenergic blockers: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Betaxolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Bisoprolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Bretylium: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class III antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Brimonidine; Timolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Bupivacaine; Lidocaine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IB antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Calcium-channel blockers: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Carbamazepine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., carbamazepine), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Carteolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Carvedilol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Chlordiazepoxide; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Class IA Antiarrhythmics: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IA antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Class IB Antiarrhythmics: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IB antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Class IC Antiarrhythmics: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IC antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Class III Antiarrhythmics: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class III antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Clevidipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Clomipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Delavirdine: (Moderate) Use caution during concurrent use of lacosamide and delavirdine, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; delavirdine is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadminsitered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Desipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Dextromethorphan; Quinidine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IA antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Digoxin: (Moderate) Lacosamide causes PR interval prolongation in some patients. Caution is advised during coadministration of lacosamide with other drugs that cause PR prolongation, such as digoxin, since further PR prolongation is possible. If concurrent use is necessary, an ECG is recommended prior to initiation of lacosamide and after the drug is titrated to the maintenence dose. Patients receiving intravenous lacosamide should be closely monitored due to the potential for profound bradycardia and AV block during coadministration.
Diltiazem: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Disopyramide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IA antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Dofetilide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class III antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Dorzolamide; Timolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Doxepin: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Dronedarone: (Moderate) Lacosamide causes PR interval prolongation in some patients. Caution is advised during coadministration of lacosamide with other drugs that cause PR prolongation, such as dronedarone, since further PR prolongation is possible. If concurrent use is necessary, an ECG is recommended prior to initiation of lacosamide and after the drug is titrated to the maintenence dose. Patients receiving intravenous lacosamide should be closely monitored due to the potential for profound bradycardia and AV block during coadministration.
Eslicarbazepine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., eslicarbazepine), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Esmolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Felbamate: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., felbamate), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Felodipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as lacosamide, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of lacosamide during coadministration with fenofibric acid.
Flecainide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IC antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Fluconazole: (Moderate) Use caution during concurrent use of lacosamide and fluconazole, particularly in patients with renal or hepatic impairment. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadministered with fluconazole. Dosage reduction of lacosamide may be necessary in this population. Lacosamide is a CYP3A4, CYP2C9, CYP2C19 substrate; fluconazole is a potent inhibitor of CYP2C19 and a moderate inhibitor of CYP3A4 and CYP2C9.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosphenytoin: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., fosphenytoin), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as lacosamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
Ibutilide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class III antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Imipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Indinavir: (Moderate) Use caution during concurrent use of lacosamide and indinavir, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; indinavir is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadminsitered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Isradipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Itraconazole: (Moderate) Use caution during concurrent use of lacosamide and itraconazole, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; itraconazole is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadministered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Ketoconazole: (Moderate) Use caution during concurrent use of lacosamide and ketoconazole, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; ketoconazole is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadminsitered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Labetalol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lamotrigine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., lamotrigine), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Letermovir: (Moderate) The plasma concentration of lacosamide may be increased during concurrent use with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. If lacosamide is administered to a patient with hepatic impairment receiving both letermovir and cyclosporine, a lacosamide dose reduction may be needed. Lacosamide is a CYP3A4 substrate. Letermovir is a moderate inhibitor of CYP3A4. However, when given with cyclosporine, the combined effect of letermovir and cyclosporine on a CYP3A4 substrate is similar to a strong CYP3A4 inhibitor.
Levamlodipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Levobunolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Levoketoconazole: (Moderate) Use caution during concurrent use of lacosamide and ketoconazole, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; ketoconazole is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadminsitered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Lidocaine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IB antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lidocaine; Epinephrine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IB antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lidocaine; Prilocaine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IB antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lopinavir; Ritonavir: (Moderate) Lacosamide causes PR interval prolongation in some patients. Caution is advised during coadministration of lacosamide with other drugs that cause PR prolongation, such as lopinavir, since further PR prolongation is possible. (Moderate) Use caution during concurrent use of lacosamide and ritonavir, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; ritonavir is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadministered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Luliconazole: (Moderate) Theoretically, luliconazole may increase the side effects of lacosamide, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of lacosamide, such as PR prolongation. Patients with renal or hepatic impairment may be particularly affected. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Maprotiline: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Mefloquine: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors. Some, but not all anticonvulsants, induce CYP3A4 and may increase the metabolism of mefloquine. Use of enzyme-inducing anticonvulsants can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria.
Metoprolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Mexiletine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IB antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Molindone: (Moderate) Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.
Nadolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Nebivolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Nebivolol; Valsartan: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Nicardipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
NIFEdipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Nimodipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Nirmatrelvir; Ritonavir: (Moderate) Use caution during concurrent use of lacosamide and ritonavir, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; ritonavir is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadministered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Nisoldipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Nortriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Oritavancin: (Moderate) Lacosamide is metabolized by CYP2C19; oritavancin is a weak CYP2C19 inhibitor. Coadministration may result in elevated lacosamide plasma concentrations. If these drugs are administered concurrently, monitor patients for signs of lacosamide toxicity, such as fainting or falling spells, low blood pressure, or changes in heart rate (fast, slow, or irregular).
Oxcarbazepine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., oxcarbazepine), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Perindopril; Amlodipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Phentermine; Topiramate: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., topiramate), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Phenytoin: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., phenytoin), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Pindolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Procainamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IA antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Prochlorperazine: (Major) The phenothiazines, including prochlorperazine, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the phenothiazine or the anticonvulsant.
Propafenone: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IC antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Propranolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Protriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Quinidine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IA antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Ritonavir: (Moderate) Use caution during concurrent use of lacosamide and ritonavir, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; ritonavir is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadministered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Rufinamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., rufinamide), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Sotalol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class III antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Telmisartan; Amlodipine: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Timolol: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Tipranavir: (Moderate) Use caution during concurrent use of lacosamide and tipranavir, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; tipranavir is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadminsitered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Topiramate: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., topiramate), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Trandolapril; Verapamil: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Trimipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Valproic Acid, Divalproex Sodium: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g.,valproic acid), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Verapamil: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Zonisamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., zonisamide), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
The exact mechanism by which lacosamide exerts its anticonvulsant effects is unknown. In vitro, lacosamide enhances slow inactivation of voltage-gated sodium channels, with subsequent stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing. Additional in vitro data indicate that lacosamide interferes with the activity of collapsin response mediator protein-2 (CRMP-2), a phosphoprotein that is involved in neuronal differentiation and control of axonal growth. The role of CRMP-2 in the control of seizures is unknown.
Lacosamide is administered orally or intravenously. The Vd of lacosamide is 0.67 L/kg with no clinically relevant protein binding (less than 15%). The hepatic enzymes primarily responsible for the formation of the major metabolite (O-desmethyl-lacosamide) are CYP2C9, CYP2C19, and CYP3A4. O-desmethyl-lacosamide has no known pharmacologic activity and a plasma exposure that is 10% of the parent compound. Approximately 95% of a dose is excreted in the urine and 0.5% in the feces as unchanged lacosamide (40%), O-desmethyl-lacosamide (30%), and a structurally unknown polar fraction (20%). The elimination half-life of unchanged lacosamide is 13 hours while the elimination half-life of the metabolite is 15 to 23 hours.
Affected cytochrome P450 enzymes and drug transporters: CYP2C9, CYP2C19, CYP3A4
In vitro data suggest that lacosamide is a CYP2C9, CYP2C19, and CYP3A4 substrate, and has the potential to inhibit CYP2C19 at therapeutic concentrations. In vitro data also indicate that lacosamide does not induce CYP1A2, CYP2B6, CYP2C9, CYP2C19, or CYP3A4, and does not inhibit CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, or CYP3A4/5.
-Route-Specific Pharmacokinetics
Oral Route
After oral administration, lacosamide is completely absorbed with negligible first-pass effect with an absolute bioavailability of approximately 100%. Maximum lacosamide plasma concentrations occur approximately 1 to 4 hours after oral dosing with the immediate-release tablet; steady-state concentrations are achieved after 3 days of twice daily repeated administration. The oral tablet and oral solution are bioequivalent. In a multiple-dose pharmacokinetic study in healthy adults, at steady-state, the peak plasma lacosamide concentration after oral administration of extended-release lacosamide was reached in 7 hours; steady-state plasma concentrations are achieved after 4 days of once daily repeated administration. Food does not affect the rate or extent of absorption.
Intravenous Route
After intravenous administration, Cmax is reached at the end of the infusion. When administered intravenously over 30 or 60 minutes, the infusion is bioequivalent to an equivalent dose of the oral tablet. After a 15-minute infusion, bioequivalence was met for AUC, but Cmax was 20% higher than that of the oral tablet.
-Special Populations
Hepatic Impairment
The AUC of lacosamide is increased by approximately 50% to 60% in patients with moderate hepatic impairment (Child-Pugh B) compared to that of healthy subjects. The pharmacokinetics of lacosamide have not been evaluated in patients with severe hepatic impairment.
Renal Impairment
The AUC of lacosamide is increased by approximately 25% in patients with mild (CrCl 50 to 80 mL/minute) to moderate (CrCl 30 to 50 mL/minute) renal impairment and by 60% in those with severe renal impairment (CrCl less than 30 mL/minute). Lacosamide is effectively removed from the plasma by hemodialysis. After a 4-hour hemodialysis treatment, the AUC is reduced by approximately 50%.
Pediatrics
For pediatric patients weighing 10 kg, 28.9 kg (the mean population body weight), and 70 kg, the typical plasma half-life of lacosamide is 7.2 hours, 10.6 hours, and 14.8 hours, respectively. Steady state plasma concentrations are achieved after 3 days of twice daily repeated administration.
Geriatric
The AUC and Cmax of lacosamide are approximately 20% higher in elderly subjects compared to younger adults.
Gender Differences
Lacosamide clinical trials indicate that sex does not have a clinically relevant influence on the pharmacokinetics of lacosamide.
Ethnic Differences
There are no clinically relevant differences in the pharmacokinetics of lacosamide between Asian, Black, and Caucasian subjects.
Other
CYP2C19 Polymorphism
There are no clinically relevant differences in the pharmacokinetics of lacosamide between CYP2C19 poor metabolizers and extensive metabolizers.