Approval date: X X X X X X X X X X X X X X
Date of revision: X X X X X X X X X X X X X X
Lacosamide Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician.
Drug Name]
Generic Name: Lacosamide Tablets
English name: Lacosamide Tablets
Hanyu Pinyin: Lakaosha′an Pian
Ingredients】The main ingredient of this product is lacosamide.
Chemical name: (R)-2-acetamido-N-phenylmethyl-3-methoxypropionamide
Chemical structure formula.
Molecular formula: C13H18N2O3
Molecular weight: 250.30
Properties
This product is a film-coated tablet, which appears white or off-white after removing the coating.
Indications
This product is indicated for the combined treatment of partial seizures in patients aged 16 years and above with epilepsy.
Specification】50mg; 100mg (based on C13H18N2O3)
Dosage]
Recommended Dosage
This product must be taken twice daily (usually once in the morning and once in the evening). The recommended starting dose is 50mg twice daily and should be increased to the initial therapeutic dose of 100mg twice daily after one week.
The starting dose may also be a single loading dose of 200 mg, followed by a maintenance dose regimen of 100 mg twice daily (200 mg/day) for approximately 12 hours. A loading dose may be given to patients when the physician determines that rapid achievement of steady-state plasma concentrations and efficacy of lacosamide is required. Considering the potential for increased incidence of CNS adverse reactions, loading doses should be administered under medical supervision (see [Adverse Reactions]). The use of loading doses in acute situations, such as persistent epilepsy, has not been studied.
Based on efficacy and tolerability, the maintenance dose may be increased weekly by 50 mg twice daily (100 mg twice weekly) until increased to the maximum recommended daily dose of 400 mg (200 mg twice daily).
If a dose of Lacosamide is missed, the patient should immediately make up the dose and then take the next dose on schedule. If the patient is found to have missed a dose within 6 hours of the time the next dose is due, the patient does not need to make up the missed dose and should simply take the next dose of Lacosamide on schedule. Patients should not take a double dose.
Based on current clinical practice, if lacosamide is to be discontinued, it is recommended that it be discontinued gradually (e.g., by tapering the daily dose to 200 mg/week).
Dosing in Special Populations
Impaired renal function
Patients with mild and moderate renal impairment (CLCR> 30 ml/min) do not require dose adjustment. Patients with mild or moderate renal impairment may be considered to receive a 200 mg loading dose, but further dose adjustments (>200 mg daily) should be made with caution. In patients with severe renal impairment (CLCR ≤ 30 ml/min) and end-stage renal disease, the recommended maximum maintenance dose is 250 mg/day, and caution should be exercised when adjusting the dose in these patients. If a loading dose is indicated, a 100 mg starting dose should be used followed by a 50 mg per dose, twice daily dosing regimen for the first week. In patients requiring hemodialysis, it is recommended that no more than 50% of the split daily dose be supplemented directly after the completion of hemodialysis. Caution should be exercised when used in patients with end-stage renal disease because of the paucity of relevant clinical experience and the potential for accumulation of metabolites (with unknown pharmacological activity).
Hepatic Impairment
The maximum recommended dose for patients with mild to moderate hepatic impairment is 300 mg/day, and dose adjustments in patients with hepatic impairment should be made with caution.
Dose adjustments should be made with caution in patients with coexisting renal impairment. The pharmacokinetics of Lacosamide have not been evaluated in patients with severe hepatic impairment (see [Pharmacokinetics]) and it is not recommended for use in patients with severe hepatic impairment.
Directions for administration
Take by mouth. This product may be taken with or without food.
[Adverse Reactions].
Summary of safety characteristics
Based on the results of a pooled analysis of combination therapy placebo-controlled clinical trials conducted in 1308 patients with partial-onset seizures, at least 1 adverse reaction was reported in 61.9% and 35.2% of patients randomly assigned to receive this product or placebo, respectively. The most frequently reported adverse reactions (≥10%) in the treatment group were dizziness, headache, nausea, and diplopia. These reactions were usually mild to moderate in severity. Some reactions were dose related and were able to resolve with dose reduction. The incidence and severity of central nervous system and gastrointestinal adverse reactions usually decreased over time.
The rate of discontinuation due to adverse reactions was 12.2% in patients randomly assigned to receive this product and 1.6% in patients randomly assigned to receive placebo in all controlled studies. The most common adverse reaction leading to discontinuation of this product was dizziness.
The incidence of central nervous system adverse reactions such as dizziness may be elevated after administration of loading doses.
Based on analysis of data from non-inferiority monotherapy clinical trials comparing lacosamide with carbamazepine extended-release, the most frequently reported adverse reactions (≥10%) to lacosamide were headache and dizziness. The discontinuation rate due to adverse reactions was 10.6% in patients treated with lacosamide compared to 15.6% in patients treated with carbamazepine extended-release.
Adverse Reaction List
The following table lists the incidence of adverse reactions reported in clinical trials and post-marketing use experience. Incidence rates are defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), unknown (incidence cannot be estimated based on available data). Within each incidence group, adverse reactions were listed in descending order of severity.
Systemic organ classification Very common Common Uncommon Unknown Blood and lymphatic system abnormalities Granulocyte deficiency
(1) Immune system abnormalities Drug
Hypersensitivity reactions
(1) Drug reactions with eosinophilia and systemic symptoms
(1, 2) Psychiatric abnormalities Depression
Mental confusion
Insomnia
(1) Aggressive behavior
(1)
Agitation
(1)
euphoria
(1)
mental abnormality
(1)
suicide attempt
(1)
suicidal ideation
(1)
hallucinations
(1) Neurological abnormalities Dizziness
Headache balance disorder
Coordination abnormalities
Memory disorders
Cognitive impairment
Drowsiness
Tremor
Nystagmus
hypesthesia
Difficulty in making sounds
Attention deficit
Abnormal sensory syncope (2) Convulsions
(3) Eye abnormalities diplopia blurred vision ear and vagus abnormalities vertigo
Tinnitus Cardiac abnormalities Atrioventricular block
(1, 2)
Bradycardia
(1, 2)
Atrial fibrillation
(1, 2)
Atrial flutter
(1, 2) Digestive system abnormalities nausea and vomiting
Constipation
Gastrointestinal distention
Indigestion
Dry mouth
Diarrhea Liver and biliary abnormalities Abnormal liver function tests
(2)
Elevated liver enzymes (>2×ULN) (1) Skin and subcutaneous tissue abnormalities Pruritus
Skin rash
(1) Angioedema
(1)
Urticaria
(1) Stevens-Johnson syndrome
(1)
toxic epidermolysis bullosa
(1) Musculoskeletal and connective tissue abnormalities Muscle spasms Generalized discomfort and site of administration abnormalities Gait disorders
Weakness
fatigue
Irritability
Sense of intoxication Complications from injury, poisoning, and medical management Falls
Skin tears
Contusions (1)
Adverse reactions reported in post-marketing use experience.
(2)
See specific adverse reaction descriptions.
(3) Adverse reactions reported in open studies.
Specific Adverse Reaction Descriptions
Use of this product may cause a dose-related prolongation of the PR interval. Adverse reactions associated with prolonged PR interval (e.g., AV block, syncope, bradycardia) may occur. In combination therapy clinical trials, the incidence of degree I AV block reported in patients with epilepsy was uncommon and was 0.7%, 0%, 0.5% and 0% in the 200 mg, 400 mg and 600 mg Benadryl and placebo groups, respectively. Atrioventricular block of degree II or greater was not observed in these studies. However, second and third degree AV block following treatment with this product has been reported in post-marketing use experience. In clinical trials of monotherapy comparing lacosamide with carbamazepine extended-release agents, PR intervals were prolonged to a comparable extent in the lacosamide and carbamazepine groups.
The occurrence of syncope was uncommon in clinical trials. There was no difference in the incidence between patients with epilepsy treated with this product (n=944) versus placebo (n=364), 0.1% versus 0.3%, respectively. In monotherapy clinical trials comparing lacosamide with carbamazepine extended-release, syncope was reported in 7/444 (1.6%) patients in the lacosamide group and in 1/442 (0.2%) patients in the carbamazepine extended-release group.
No atrial fibrillation or atrial flutter was reported in short-term clinical trials; however, atrial fibrillation or atrial flutter was reported in open epilepsy trials and postmarketing use experience.
Abnormal laboratory tests
Abnormal liver function tests were observed in controlled trials of this product in adult patients with partial-onset seizures who were receiving one to three combined antiepileptic drugs. The incidence of ALT elevation to ≥3XULN was 0.7% (7/935) in patients in the Benadryl-treated group compared with 0 (0/356) in the placebo group.
Multi-organ hypersensitivity reactions
Multiorgan hypersensitivity reactions (also known as eosinophilia and systemic symptoms of drug reactions) have been reported in patients treated with certain antiepileptic drugs. The presentation of these reactions varies, but they generally present as fever and rash and may be associated with involvement of different organ systems. If a multi-organ hypersensitivity reaction is suspected, lacosamide should be discontinued.
Pediatric population
The incidence, type and severity of adverse reactions in adolescents aged 16 to 18 years are expected to be the same as in adults. The safety of this product in children under 16 years of age is not known.
Geriatric Population
In monotherapy studies comparing lacosamide with carbamazepine extended-release, the types of adverse reactions associated with lacosamide in elderly patients (≥ 65 years of age) appeared to be similar to those in patients younger than 65 years of age. However, higher rates of falls, diarrhea, and tremor were reported in older patients than (≥5% difference) in younger adult patients. The most frequently reported cardiac-related adverse reaction in older patients compared with the younger adult population was first-degree AV block, reported in 4.8% (3/62) of the lacosamide group in older patients compared with 1.6% (6/382) in younger adult patients. The discontinuation rate for adverse events was 21.0% (13/62) in the lacosamide group in older patients compared with 9.2% (35/382) in younger adult patients. These differences between elderly patients and younger adult patients were similar to those in the positive control group.
Reports of Suspected Adverse Reactions
It is important to report suspected adverse reactions after marketing approval of this product. This allows for ongoing monitoring of the benefit/risk ratio of this product. Health care professionals are required to report suspected adverse reactions through the appropriate reporting system.
[Contraindication].
Contraindicated in persons with hypersensitivity to the active ingredient or to any of the excipients in this product.
Contraindicated in individuals with known atrioventricular block of the second or third degree.
Precautions]
Suicidal ideation and behavior
Suicidal ideation and behavior have been reported in patients receiving antiepileptic drugs for multiple indications. A meta-analysis of randomized, placebo-controlled trials of antiepileptic drugs has also demonstrated a small increase in the risk of suicidal ideation and behavior. The mechanism of this risk is unclear, and the available data do not rule out the possibility that lacosamide increases this risk. Therefore, patients should be monitored for signs of suicidal ideation and behavior, and appropriate treatment should be considered. Patients (and patients’ caregivers) should be advised to seek medical advice if signs of suicidal ideation or behavior develop (see [ADVERSE REACTIONS]).
Heart Rhythm and Cardiac Conduction
A dose-related prolongation of the PR interval has been observed with this product in clinical studies. This product should be used with caution in patients with known conduction problems, severe cardiac disease (e.g., myocardial infarction or heart failure), in the elderly, or in combination with drugs that can cause prolongation of the PR interval.
Second-degree or greater AV block has been reported in post-marketing use experience. No atrial fibrillation or atrial flutter was reported in placebo-controlled trials of this product in patients with epilepsy; however, atrial fibrillation and atrial flutter have been reported in open epilepsy trials and in postmarketing use experience (see [Adverse Reactions]).
Patients should be made aware of symptoms of atrioventricular block of degree II or greater (e.g., slowed or irregular pulse, light-headedness, and feeling of fainting) and symptoms of atrial fibrillation and atrial flutter (e.g., palpitations, rapid or irregular pulse, shortness of breath). Patients should be advised to seek medical advice if these symptoms occur.
Dizziness
Treatment with this product can cause dizziness, which may increase the incidence of accidental injury or falls. Therefore, patients should be advised to use caution until they are familiar with the potential effects of this product (see [ADVERSE REACTIONS]).
Effects on the ability to drive and operate machinery
This product may have a mild to moderate effect on the ability to drive and operate machinery. Treatment with this product may cause dizziness or blurred vision. Therefore, patients should be advised not to drive or operate other potentially hazardous machinery.
[For pregnant and lactating women].
Pregnancy
Risks associated with epilepsy and overall antiepileptic drugs
All antiepileptic drug studies have shown that the prevalence of malformations in the offspring of women treated for epilepsy is two to three times higher than in the general population, with an incidence of approximately 3% in the general population. In the treated population, multiple drugs have been observed to cause an increase in malformations, but it remains unclear to what extent treatment and/or disease play a role in this.
In addition, effective antiepileptic drug therapy should not be interrupted because exacerbation of the disease is harmful to both the mother and the fetus.
Risks associated with Lacosamide
There are insufficient data on the use of this product in pregnant women. Animal studies have not suggested teratogenic effects in rats or rabbits, but embryotoxicity has been observed in rats and rabbits at maternal toxicity dose levels (see [Pharmacologic Toxicology]). The potential risk of this product in humans is unknown.
This product should not be used during pregnancy unless clearly needed (if the benefit to the mother outweighs the potential risk to the fetus). If a woman decides to become pregnant, the use of this product should be carefully reevaluated.
Lactation
It is unknown whether lacosamide is secreted into human breast milk and risks to the newborn/infant cannot be excluded. Animal studies have shown that lacosamide is secreted into breast milk. As a precautionary measure, breastfeeding should be discontinued during treatment with this product.
Fertility
No adverse effects on fertility or reproduction were observed in male or female rats at plasma exposures (AUC) of approximately two times the maximum recommended human dose (MRHD) plasma exposure achieved in rats.
[Pediatric Use].
The safety and efficacy of this product for the treatment of children under 16 years of age are not known.
Geriatric Use]
No dose reduction is required in elderly patients (age over 65 years). There is limited experience with the use of this product in elderly patients with epilepsy. Age-related decreased renal clearance and increased AUC levels should be considered when used in elderly patients (see “Impaired Renal Function” and “Pharmacokinetics” under [Dosage]).
Drug Interactions]
This product should be used with caution in patients treated with drugs known to cause prolonged PR intervals (e.g., carbamazepine, lamotrigine, eslicarbazepine, pregabalin) and in patients treated with class I antiarrhythmic drugs. However, subgroup analysis of clinical trials did not reveal an increase in the magnitude of PR interval prolongation in patients receiving the combined administration of carbamazepine or lamotrigine.
In Vitro Trial Data
The data overall suggest that lacosamide has a low potential for drug interactions. Multiple in vitro studies have demonstrated that lacosamide does not induce CYP1A2, CYP2B6, and CYP2C9 enzymes and does not inhibit CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6, and CYP2E1 enzymes over the range of blood concentrations observed in clinical trials. An in vitro study showed that lacosamide is not transported via P-glycoprotein in the intestine. In vitro data show that CYP2C9, CYP2C19 and CYP3A4 catalyze the formation of O-demethyl metabolites.
In vivo test data
The extent to which lacosamide inhibits or induces CYP2C19 and CYP3A4 is not clinically significant. Lacosamide did not affect the AUC of midazolam (metabolized by CYP3A4; lacosamide was administered at a dose of 200 mg twice daily), but the Cmax of midazolam was slightly elevated (30%). Lacosamide did not affect the pharmacokinetics of omeprazole (metabolized by CYP2C19 and CYP3A4, with lacosamide administered at a dose of 300 mg per dose, twice daily).
The CYP2C19 inhibitor omeprazole (40 mg per dose, once daily) did not cause clinically meaningful changes in lacosamide exposure. Therefore, it is unlikely that a moderate inhibitor of CYP2C19 would have a clinically meaningful effect on systemic exposure to lacosamide.
Combination therapy with CYP2C9 potent inhibitors (e.g., fluconazole) and CYP3A4 potent inhibitors (e.g., itraconazole, ketoconazole, ritonavir, clarithromycin) may result in increased systemic exposure to lacosamide and caution is advised when using them. Such interactions have not been identified in in vivo trials, but may occur based on in vitro trial data.
Potent enzyme inducers such as rifampicin or St. John’s Wort (Kanzai) may moderately reduce systemic exposure to lacosamide. Therefore, caution should be exercised when starting or ending treatment with these enzyme inducers.
Antiepileptic drugs
In interaction tests, lacosamide did not significantly affect plasma concentrations of carbamazepine and valproic acid. Lacosamide plasma concentrations were unaffected by carbamazepine and valproic acid. Results of a population pharmacokinetic analysis showed a 25% reduction in total systemic exposure to lacosamide after combined treatment with other antiepileptic drugs known to be enzyme inducers (various doses of carbamazepine, phenytoin, phenobarbital).
Oral contraceptives
In an interaction trial, no clinically meaningful interactions occurred between lacosamide and the oral contraceptives ethinylestradiol and levonorgestrel. Progesterone concentrations were not affected when these drugs were combined.
Other drugs
Interaction tests have shown that lacosamide does not affect the pharmacokinetics of digoxin. Lacosamide does not interact with metformin in a clinically meaningful manner.
Coadministration of warfarin with lacosamide does not result in clinically meaningful changes in the pharmacokinetics or pharmacodynamics of warfarin.
Although no pharmacokinetic interaction data were obtained for lacosamide with alcohol, an effect of alcohol on pharmacodynamics cannot be excluded.
The protein binding rate of lacosamide is low, less than 15%. Therefore, it is considered unlikely that clinically meaningful interactions with other drugs will occur through competition for protein-binding sites.
[Drug Overdose].
Clinical symptoms
Symptoms observed after accidental or intentional overdose of Lacosamide are mainly related to the central nervous system and gastrointestinal system.
The types of adverse reactions that occurred after patient exposure to 400 mg to 800 mg of lacosamide were not clinically different from the types of adverse reactions that occurred after patient exposure to the recommended dose of lacosamide.
The reactions reported after ingestion of doses greater than 800 mg were dizziness, nausea, vomiting, and seizures (generalized tonic clonic seizures, seizure continuity). Cardiac conduction disturbances, shock, and coma have also been observed. Patient deaths have been reported after a single acute overdose of several grams of Lacosamide.
Treatment
There is no specific antidote for lacosamide overdose. Treatment of lacosamide overdose should include systemic supportive measures, including hemodialysis if necessary (see [Pharmacokinetics]).
Pharmacology and Toxicology
Pharmacological effects
The exact mechanism by which lacosamide exerts its antiepileptic effects in humans has not been fully elucidated. In vitro electrophysiological studies have shown that lacosamide selectively enhances the slow inactivation of voltage-gated sodium channels, thereby stabilizing hyperexcitable neuronal cell membranes and inhibiting repetitive neuronal firing.
Toxicological studies
Genotoxicity
The Ames test for lacosamide and the in vivo micronucleus test in mice were negative, and the in vitro lymphoma test in mice was positive.
Reproductive toxicity
No adverse effects on male or female fertility or reproduction were observed in rats given lacosamide orally at doses that produced plasma exposures (AUC) up to approximately twice the exposure produced by the maximum recommended human dose (MRHD) of 400 mg/day.
Oral administration of lacosamide (20, 75, 200 mg/kg/day in rats and 6.25, 12.5, 25 mg/kg/day in rabbits) during organogenesis in pregnant rats and rabbits did not produce teratogenic effects; however, the maximum administered dose was limited by maternal toxicity in both species and embryo-fetal mortality in rats. In rats and rabbits, these doses induced maternal plasma exposures (AUC) approximately twice and one time the exposures produced by MRHD, respectively.
In rats, lacosamide (25, 70, 200 mg/kg/day) was administered orally from day 7 of gestation to day 20 of lactation, and increased perinatal mortality and weight loss in the offspring were observed at the highest dose. The nonresponsive dose (70 mg/kg/day) for perinatal developmental toxicity in rats produced maternal plasma exposure (AUC) approximately equal to that produced by MRHD.
Oral administration of lacosamide (30, 90, 180 mg/kg/day) in rats during neonatal and juvenile periods resulted in reduced brain weight and long-term neurobehavioral changes (altered absentee behavior, learning memory deficits). It is generally accepted that the early postnatal period in rats corresponds to the late human gestation period in terms of brain development. The unresponsive dose of developmental neurotoxicity in rats produces maternal plasma exposure (AUC) approximately equal to 0.5 times the exposure produced by MRHD.
In vitro tests have shown that lacosamide interferes with the activity of cerebral decay response regulatory protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential adverse effects related to the development of the central nervous system cannot be ruled out.
Carcinogenicity
No drug-related carcinogenicity was observed in mice and rats given lacosamide orally once daily for 104 weeks at doses that produced plasma exposures (AUC) up to approximately one and three times the exposure produced by the maximum recommended human dose (MRHD) of 400 mg/day, respectively.
[Pharmacokinetics].
Absorption
After oral administration, lacosamide is rapidly and completely absorbed. The oral bioavailability of lacosamide tablets is approximately 100%. The plasma concentration of the prototype lacosamide increases rapidly after oral administration, reaching Cmax approximately 0.5 to 4 hr after administration. food does not affect the rate or extent of absorption.
Distribution
The volume of distribution is approximately 0.6 L/kg. lacosamide is less than 15% bound to plasma proteins.
Metabolism
95% of the dose is excreted in the urine as lacosamide prototype and metabolites. The metabolic profile of lacosamide is not fully understood.
The major compound excreted via urine is the prototype lacosamide (approximately 40% of the dose), with its O-demethyl metabolite less than 30%.
In urine, the polar fraction, which is considered to be a serine derivative, accounts for about 20%, but only small amounts (0-2%) of such substances were detected in the plasma of some subjects. Small amounts (0.5-2%) of other metabolites were found in urine.
Data from in vitro tests showed that CYP2C9, CYP2C19 and CYP3A4 are able to catalyze the formation of O-demetabolites, but the isoenzymes that play a major role were not identified in in vivo tests. When comparing the pharmacokinetics of lacosamide in strong metabolizers (containing functional CYP2C19) and weak metabolizers (lacking functional CYP2C19), clinically meaningful differences in lacosamide exposure between the two were not observed. In addition, interaction tests with omeprazole (a CYP2C19 inhibitor) showed no clinically meaningful changes in lacosamide plasma concentrations, suggesting that this pathway is of lesser importance. Plasma concentrations of O-desmethyl lacosamide are approximately 15% of lacosamide plasma concentrations. The major metabolite is known to have no pharmacological activity.
Clearance
Lacosamide is cleared from the systemic circulation primarily by renal excretion and biotransformation. Following oral and intravenous administration of radiolabeled lacosamide, approximately 95% of the radioactively administered drug is recovered in the urine and less than 0.5% in the feces. The clearance half-life of the prototype lacosamide is approximately 13 hours. Pharmacokinetics are proportional to dose and remain constant over time, with low intra- and inter-subject variability. Steady-state blood concentrations were reached after 3 days of twice-daily dosing. The cumulative factor at elevated blood concentrations was approximately 2.
Steady-state concentrations at a single loading dose of 200 mg approximated steady-state concentrations at 100 mg per dose, administered orally twice daily.
Pharmacokinetics in Special Patient Populations
Gender
Clinical trials have shown no clinically significant effect of gender on lacosamide plasma concentrations.
Impaired Renal Function
Compared to healthy subjects, lacosamide AUC is increased by approximately 30% in patients with mild and moderate renal impairment and by approximately 60% in patients with severe renal impairment and in patients with end-stage renal disease requiring hemodialysis, while Cmax is not affected.
Hemodialysis effectively removes lacosamide from plasma. lacosamide AUC is reduced by approximately 50% after 4 hours of hemodialysis treatment. Therefore, supplemental dosing after hemodialysis is recommended (see [Dosage]). Exposure to O-demethyl metabolites is elevated several-fold in patients with moderate and severe renal impairment. Levels of O-demethyl metabolites were elevated in patients with end-stage renal disease when not receiving hemodialysis and continued to be elevated during the 24-hour sampling period. It is not clear whether increased metabolite exposure in subjects with end-stage renal disease causes adverse effects, but it was determined that the metabolite was not pharmacologically active.
Impaired liver function
Subjects with moderate hepatic impairment (Child-Pugh B) had elevated lacosamide plasma concentrations (approximately 50% elevated AUCnorm). This elevated exposure was due in part to decreased renal function in the subjects studied. Estimated non-renal clearance was decreased in subjects in the study resulting in a 20% elevation in lacosamide AUC. The pharmacokinetics of lacosamide have not been evaluated in patients with severe hepatic impairment (see [DOSAGE]).
Geriatric patients (age over 65 years)
In a study of older men and women (including four > 75-year-old patients), the AUC was approximately 30% and 50% higher than in younger men, respectively. This was partly due to lower body weight. Weight-standardized differences were 26% and 23%, respectively. Increased exposure variability was also observed. Renal clearance of lacosamide was only slightly decreased in the older subjects of the study.
Dose reduction is not considered generally necessary unless required due to decreased renal function (see [DOSAGE AND ADMINISTRATION]).
Storage]
Store in a sealed container at a temperature not exceeding 30°C.
Packaging
Aluminum-plastic (aluminum foil for pharmaceutical packaging (PTP) and polyvinyl chloride/polyvinylidene chloride composite rigid sheet (PVC/PVDC)) packaging.
14 tablets/plate x 4 plates/box.
【Expiration date】 18 months.
Execution Standard
Approval number】
【Manufacturer】
Enterprise name: Jiangxi Qingfeng Pharmaceutical Co.
Production Address: Shahe Industrial Park, Ganzhou City, Jiangxi Province
Postal Code: 341000
Telephone number: 400-882-6066 (sales) 0797-7020096 (quality)
Fax number: 0797-5560615