Cenobamate - Uses, Dosage, Interactions, Side Effects, and Precautions

Overview

Epilepsy is a widely known condition of the neurological system of the body that results in several kinds of seizures. One of the well-known and recurrently occurring seizures is partial-onset. Cenobamate is composed of a state-of-the-art tetrazole-derived compound with a single chiral apex. Cenobamate promises to show a marked reduction in the repetitive pattern of neuronal firing with the help of enhancing the inactivation of fast or slow sodium channels. This is additionally achieved by inhibiting the component that is persistent in sodium current.

Cenobamat is a drug that has been put forward as a treatment option for adult patients who have been diagnosed with partial-onset seizures or POS. Partial-onset seizures are known to be one of the most common kinds of epileptic seizures. Seizures halt the quality of a patient’s life. In addition to this, the patient’s overall health is always at risk of developing several underlying medical conditions. Loss of consciousness is one of the major symptoms of partial-onset seizures. Rarely, partial-onset seizures can pose a threat to the patient’s life. On the other hand, partial-onset seizures also pose a higher frequency for sudden unexpected death in epilepsy or SUDEP.

Kindling refers to the biological process of the repeated firing of impaired electrical impulses. In the beginning, kindling does not cause any harm, but after frequent episodes, kindling may progress a disease more quickly and promote several dangerous symptoms. It is due to kindling that frequent episodes of partial-onset seizures lead to the progression of epilepsy. The outcome of epilepsy may not immediately lead to the patient’s death, nonetheless, the quality of the patient’s life is highly reduced. As of today, there are over twenty approved anti-seizure and antiepileptic drugs for the treatment of partial-onset seizures. Unfortunately, the majority of these approved drugs do not respond to the disease well enough and are thus refractory.

Cenobamate is an advanced compound that is derived from tetrazole and has proved to decrease the repetition of neuronal firing due to enhancement of the inactivation of the sodium channels, both fast and slow as well as reducing the component that is persistent in sodium current. In addition to this, Cenobamate is a pragmatic allosteric modulator of six sub-categories of γ-aminobutyric acid ion channels. The exact mechanism of action of Cenobamate against partial-onset seizures still remains unclear.

The effectiveness of Cenobamate was laid down by the outcome of two well-controlled and adequate clinical trials. The trials were randomized, double-blind, multicenter, parallel-group, and included international participants. The clinical trials used an eight-week prospective baseline in order to establish the patient’s baseline frequency of twenty-eight days of seizures. The aim of both these trials was a relative comparison between the changes in the twenty-eight-day period of the percentage of frequency of seizures in the treatment span and baseline span as against the placebo. There was a significant differentiation in the treatment and the placebo arms of the twenty-eight-day period regarding the same. The treatment group had shown a fifty-six percent reduction in the frequency of seizure episodes throughout the twenty-eight-day period.

There had been three cases of DRESS or Drug Reaction with Eosinophilia and System Symptoms. These were observed during the development of Cenobamate. There has been a single fatal case of a healthy participant during the safety trials of Phase 1. DRESS or Drug Reaction with Eosinophilia and System Symptoms is highly fatal and has the potential to create a severe hypersensitivity reaction in the body. The onset of Drug Reaction with Eosinophilia and System Symptoms may begin within two to eight weeks of drug administration or after the therapy with the particular drug has been initiated. Anticonvulsants such as phenytoin, carbamazepine, and lamotrigine are more prone to developing reactions such as Drug Reaction with Eosinophilia and System Symptoms. It was suspected that Drug Reaction with Eosinophilia and System Symptoms can possibly be canceled if the drug is administered at a lower level. To know the outcome of the same, around one thousand participants were given Cenobamate as a lower dose. This particular study was for twelve months. There was no appearance of any case with Drug Reaction with Eosinophilia and System Symptoms which suggested that, at a lower level of drug in the initial stages, the maximum percentage of developing Drug Reaction with Eosinophilia and System Symptoms is no more than 0.3.

Mentioned below are the several conditions that can be the potential outcome of DRESS or Drug Reaction with Eosinophilia and System Symptoms.

• High-grade fever.

• Rashes all over the body.

• Lymphadenopathy.

• Eosinophilia.

• Abnormal functioning of the liver.

• Atypical lymphocytes.

• Leukocytosis.

Other serious risks that had been identified during the development of Cenobamate are mentioned as follows.

• Abnormality in the heart rhythm.

• Malfunctioning of the central nervous system.

• Fatigue.

• Somnolence.

• Disturbances in gait.

• Dizziness.

• Alterations in visuals.

• Cognitive impairment.

• Suicidal intentions and behaviors.

• Elevations in the liver enzyme.

• Infection of the appendix.

• Altered levels of potassium.

Cenobamate for Doctors:

Cenobamat is a drug that has been put forward as a treatment option for adult patients who have been diagnosed with partial-onset seizures or POS. Cenobamate is composed of a state-of-the-art tetrazole-derived compound with a single chiral apex. Cenobamate promises to show a marked reduction in the repetitive pattern of neuronal firing with the help of enhancing the inactivation of fast or slow sodium channels. This is additionally achieved by inhibiting the component that is persistent in sodium current.

What Is the Indication and Contraindications of Cenobamate?

Cenobamate has been indicated as a treatment option for patients suffering from partial-onset seizures.

Drugs are contraindicated in a few patients who are suffering from a particular condition or patients who are prone to developing health risks.

Mentioned below are the contraindications of Cenobamate.

• History of hypersensitivity reaction to Cenobamate.

• Allergies with the inactive ingredients of Cenobamate.

• Patients with a family history of short QT syndrome.

What Are the Administrative and Usage Instructions of Cenobamate?

Cenobamate can be administered at any time of the day. It can be taken with food or without food. A Cenobamate tablet should not be crushed or chewed. The tablet is meant to be swallowed as a whole.

Administration:

A Cenobamate tablet is taken via the oral route. It should be swallowed as a whole with water and must not be crushed or chewed. Cenobamate can be taken before or after food. Patients must strictly follow the dose prescribed by the healthcare provider. Cenobamate must not be abruptly stopped. In case a dose of Cenobamate is missed, patients are expected to contact their respective healthcare providers.

Storage and Handling:

Cenibamate tablets must be stored at a controlled room temperature ranging from twenty degrees celsius to twenty-five degrees celsius or sixty-eight degrees Fahrenheit to seventy-seven degrees Fahrenheit. The permitted excursions range from fifteen degrees celsius to thirty degrees celsius or fifty-nine degrees Fahrenheit to eighty-six degrees Fahrenheit. Cenobamate must be kept out of the reach of children.

What Are the General Dosing Recommendations for Cenobamate?

Strengths and Dosage Forms of Cenobamate

Cenobamate is available in the market in several shapes, strengths, and colors. Mentioned below are the strengths and dosage forms of Cenobamate.

• An uncoated, white, and round tablet of strength 12.5 mg.

• An uncoated, off-white, and round tablet of strength 12.5 mg.

• A film-coated, brown, and round tablet of strength 25 mg.

• A film-coated, yellow, and round tablet of strength 25 mg.

• A film-coated, brown, and round tablet of strength 100 mg.

• A film-coated, light orange, and round tablet of strength 150 mg.

• A film-coated, light orange, and oval tablet of strength 200 mg.

Cenobamate is given once a day via the oral route. Patients must strictly eat the prescribed dose and health care professionals too religiously suggest the recommended dosage because of the risk of development of allergies and severe adverse reactions.

Mentioned below are the general dosing recommendations for Cenobamate.

• The initial dose for week one and week two is 12.5 mg to be given once a day.

• The titration regimen includes week three to week four, week five to week six, week seven to week eight, and week nine to week ten.

• Week three and week four include 25 mg to be given once a day.

• Week five and week six include 50 mg to be given once a day.

• Week seven and week eight include 100 mg to be given once a day.

• Week nine and week ten include 150 mg to be given once a day.

• The maintenance dose begins from week eleven.

• Week eleven and henceforth includes a dosage of 200 mg to be given once a day.

• In case there is a need to increase the dosage, it is allowed to go above 200 mg to be given once a day, only by increments of 50 mg to be given once a day, every two weeks.

• The final maximum dose can be 400 mg to be given once a day.

Dosage Modification of Cenobamate in Patients Suffering From Hepatic Impairment:

Patients who are known to be suffering from certain conditions or impairments of the hepatic or hepato-biliary system, ranging from mild to moderate severity and with a Child-Pugh assessment point of five to nine, are advised to not exceed the dose of Cenobamate above 200 mg to be taken once a day. Patients suffering from severe hepatic impairment must not be prescribed Cenobamate.

Discontinuation:

In case Cenobamate is abruptly discontinued, the respective dose should be tapered over a span of two weeks minimum. If there is a medical emergency that requires Cenobamate to be discontinued permanently, abrupt withdrawal of the drug can be considered.

What Are the Adverse Reactions and Precautions of Cenobamate?

Cenobamate has certain precautions that need to be taken into consideration before being suggested. A detailed medical history along with family history must be studied, as well as the patient’s present clinical manifestations.

Mentioned below are the warnings and precautions of Cenobamate.

• Drug Reaction With Eosinophilia and Systemic Symptoms or Multiorgan Hypersensitivity:

DRESS or Drug Reaction with Eosinophilia and Systemic Symptoms is a kind of multiorgan hypersensitivity that has been revealed in patients who are under therapy with Cenobamate. One fatal case of Drug Reaction with Eosinophilia and Systemic Symptoms had been reported with Cenobamate. The death had occurred because Cenobamate was administered without the appropriate dosage. This particular result does not establish the fact that at a lower dose of titration, Cenobamate does not lead to Drug Reaction with Eosinophilia and Systemic Symptoms or multiorgan hypersensitivity.

Mentioned below are the clinical manifestations of a patient suffering from Drug Reaction with Eosinophilia and Systemic Symptoms or multiorgan hypersensitivity.

• Hepatitis.

• Swelling of the face.

• High-grade fever.

• Rashes all over the body.

• Myocarditis.

• Nephritis.

• Myositis.

• Acute infections.

• Viral infection.

• Lymphadenopathy.

• Eosinophilia.

• Hypersensitivity.

• Shortening of the QT Interval:

In the trials and studies that were conducted to understand Cenobamate, a great number of participants who underwent therapy with Cenobamate displayed a shortening of the QT interval. The mean reduction in the QT interval was not below 300 msec. Patients who have a family history of short QT syndrome are prone to a higher risk of sudden collapse and death as well as episodes of ventricular arrhythmias such as ventricular fibrillation. Thus such patients with a family history of short QT syndrome must not be prescribed Cenobamate in order to avoid any kind of synergistic effect of the QT interval.

• Ideation and Suicidal Behavior:

It is a well-known fact that any antiepileptic or seizure medication poses a risk of developing depression and suicidal tendencies in patients. Cenobamate too has proven to show an increased risk of suicidal behavior and ideation. Patients who are under treatment with Cenobamate must be strictly monitored for any altered behavior patterns or wild mood swings. A patient who is already suffering from depression may suffer from worsening depressive symptoms and instability of senses. The clinical trials and studies done on Cenobamate do not show a significant amount of suicidal endings. Nevertheless, it should be noted that ideation and suicidal behavior had been majorly seen in patients who are already suffering from psychosis, depression, or any other seizure and epilepsy-related neurological disorder.

• Fatigue and Somnolence:

Cenobamate leads to an escalation in fatigue and somnolence-related reactions. The increase in such symptoms and reactions is directly proportional to the dose of Cenobamate.

Mentioned below are the clinical manifestations that are seen in patients suffering from fatigue and somnolence due to Cenobamate.

• Malaise.

• Sedation.

• Fatigue.

• Hypersomnia.

• Lethargy.

• Asthenia.

• Somnolence.

• Disturbances in Coordination, Gait, and Dizziness:

Cenobamate leads to an escalation in gait abnormalities and dizziness. Patients undergoing therapy with Cenobamate must not be allowed to handle heavy machineries such as driving cars or other heavy pieces of equipment.

Mentioned below are the several disturbances in coordination, gait, and dizziness observed in patients under treatment with Cenobamate.

• Vertigo.

• Ataxia.

• Abnormalities in coordination.

• Dizziness.

• Balance disorders.

• Nystagmus.

• Disturbances in gait.

• Cognitive Dysfunction:

Cenobamate leads to the development of several malfunctioning cognitive aspects of the patient. It should be noted that, in the studies conducted, there were no serious end results due to any of the cognitive dysfunction produced by the effect of Cenobamate.

Mentioned below are a few of the cognitive dysfunctions of Cenobamate.

• Aphasia.

• Impairment in memory functions.

• Amnesia.

• Not able to concentrate.

• Lack of attention.

• Short attention span.

• Disorientation.

• State of mental confusion.

• Retardation of psychomotor signals.

• Slow process of thought formation.

• Disorders in speech.

• Mental impairment.

• Visual Disturbances:

Cenobamate leads to visual disturbances such as blurred vision, diplopia, and impaired sight. There were no severe alterations and impairment in the individuals who underwent therapy with Cenobamate or any other permanent visual changes. In the clinical trials, merely 0.5 % of the participants had to discontinue Cenobamate due to visual disturbances.

What Are the Clinical Trials Done on Cenobamate?

Clinical trials and studies of Cenobamate have been done under a wide range of several conditions as well as durations. Thus, the adverse effects observed in the trials may not be directly proportional to the frequencies of adverse effects observed in practice.

• All the trials on Cenobamate were a combination of controlled and uncontrolled adult epileptic patients suffering from a partial-onset seizure.

• The median length of the trial was eighteen weeks.

• Forty-nine percent of the participants were male with seventy-six percent caucasian.

• The average age was thirty-nine years.

• Cenobamate was administered as a therapeutic medication in one thousand nine hundred and forty-four patients.

• One thousand five hundred and seventy-five patients out of those who participated underwent the treatment with Cenobamate for a minimum of three months.

• Seven hundred and ten participants underwent the treatment with Cenobamate for twelve months.

• Three hundred and forty-nine participants underwent the treatment with Cenbamata for a minimum of twenty-four months.

• Three hundred and twenty participants underwent the treatment with Cenobamate for thirty-six months.

• Four hundred and forty-two patients were treated with Cenobamate and two hundred and sixteen patients were treated with a placebo.

• Six hundred and fifty-eight patients comprised the safety population in the pooled study of a placebo-controlled trial in patients suffering from partial-onset seizures.

• The adverse effects of Cenobamate occurred in seventy-seven percent of patients treated with Cenobamate as against the sixty-eight percent of patients treated with placebo.

Mentioned below are a few of the most common adverse events observed in the trials of Cenobamate.

• Dizziness.

• Somnolence.

• Fatigue.

• Diplopia.

• Headache.

• Ataxia.

• Nystagmus.

• Vertigo.

• Appendicitis.

• Gastrointestinal disturbances.

Mentioned below are the abnormalities in the laboratory findings of the participants.

• Three-fold increase of post-baseline elevation of alanine aminotransferase or ALT.

• A maximum elevation of alanine aminotransferase of seven folds was observed in patients under 400 mg of Cenobamate.

• An increase in the potassium levels as compared to standard baseline values of potassium.

What Are the Pharmacokinetic Drug Interactions of Cenobamate?

Cenobamate has several effects on other drugs. Mentioned below are the pharmacokinetic drug interactions of Cenobamate.

• Lamotrigine interactions with Cenobamate result in a decrease in plasma concentrations. This is because of the potential Cenobamate possesses in decreasing the efficiency of Lamotrigine.

• Carbamazepine interactions with Cenobamate result in a decrease in plasma concentrations due to the potential of Cenobamate in reducing the effectiveness of Carbamazepine.

• Phenytoin interactions with Cenobamate result in an increase in plasma concentration because of the two-fold elevation in Phenytoin levels.

• Phenobarbital and Desmethylclobazam, which is Clobazam’s active metabolite, as well as CYP2C19 substrates, interact with Cenobamate and result in an increase in plasma concentrations due to a potential for a greater risk of adverse effects from them.

• Oral contraceptives decrease the plasma concentration when they interact with Cenobamate due to the decrease in the effectiveness of oral contraceptives. In such cases, additional non-hormonal alternatives or birth control pills must be used as prescribed.

• CYP2B6 and CYP3A substrates interact with Cenobamate and result in a decrease in the plasma concentration because of the potential for decreased efficacy of these particular drugs.

• In case the patient is on medications that shorten the QT interval, caution must be taken while using Cenobamate because of its potential of shortening the QT interval.

• Patients under therapy with central nervous system depressants are at a higher risk of developing neurological reactions such as somnolence and sedation because of the concomitant use of Cenobamate.

Is Cenobamate Safe?

Pregnancy:

The data to establish clear evidence of the safety of Cenobamate in pregnant patients is not available because of the inadequate study conducted on the developmental risk of the fetus in pregnant women undergoing treatment with Cenobamate. In lab animals, administration of Cenobamate while pregnancy leads to an increase in embryofetal mortality rate and a decrease in the fetal birth weight. There was also the presence of neurobehavioral impairment along with reproductive impairment even at clinically sound drug doses. At the highest dose of Cenobamate ever tested, the fetal development of the skeletal system in addition to the ossification was nearly completely absent. A slight increase in visceral malformations was also seen at this particular dose. An increased amount of embryofetal deaths led to the teratogenic potential of Cenobamate not being studied. Thus resulting inadequate and insufficient data on embryonic development.

Mentioned below are the embryonic changes observed in pregnant lab animals under Cenobamate therapy.

• Increased rate of fetal death during the stage of organogenesis.

• Maternal toxicity.

• Neurobehavioral malfunctioning.

• Deficiency in learning pattern.

• Lack of memory.

• An increase in response to auditory startle.

• A loss in the bodyweight of the fetus.

• Weaning of the fetus.

• Reduction in the amount of corpora lutea.

• Impaired functioning of the reproductive system which resulted in decreased implantations and live embryos.

• Adverse effects in the prenatal and postnatal development of the embryo.

Lactation:

There is no clinical data that is sufficient to establish the safety of Cenobamate in lactating and nursing females. The reaction of the breast milk in infants and the effect of the drug in human milk need to be taken into consideration along with the requirement of Cenobamate in females during lactation.

Pediatric Patients:

The effectiveness and safety of Cenobamate in the pediatric group of patients have not been yet established. Juvenile animals had been studied under the administration of Cenobamate.

Mentioned below are the adverse reactions and effects of Cenobamate in juvenile animals.

• Delayed maturity of the reproductive system.

• Mortality.

• Decrease in neurological grip strength.

• Deficiency in memory.

• Inability to understand and learn.

• Neurological and neurobehavioral deficit.

• Decrease in sperm count.

• Abnormal weight of the brain.

• Impairment in the ocular histopathology.

The was a marked recovery after Cenobamate was abruptly discontinued to the extent of no presence of any adverse effects. There was no identification of an adverse reaction by a no-effect dose of Cenobamate.

Geriatric Patients:

The clinical trials of Cenobamate do not include a sufficient amount of patients in the geriatric group and thus there is no established safety and effectiveness of Cenobamate in geriatric patients. The selection of doses for elderly patients must be done with caution. The initial dose must be of the lower end. In addition to this, the patient’s renal sufficiency, hepatic function, cardiovascular function, and presence of any other disease must be taken into consideration.

Patients With Hepatic and Renal Diseases:

Cenobamate should be administered at a reduced dose in patients suffering from mild to moderate renal or hepatic impairment. Caution related to the dosage of Cenobamate must be taken while administering the drug in patients suffering from severe nature of systemic impairments. Patients in the end stage of renal disease must not undergo therapy with Cenobamate. In addition to this, patients suffering from severe impairment of the hepatobiliary system are suggested to avoid treatment with Cenobamate.

Drug Abuse Possibility:

Drug abuse refers to the term intentional and non-therapeutic administration of the drug. The aim of drug abuse is a positive physiological or psychological effect. A single dose of 400 mg of Cenobamate is likely to develop a positive attitude towards the drug such as liking the drug or a desire to take the drug again, as observed in the clinical trials and studies of Cenobamate. A mood of euphoria was observed in these patients. As the dose was increased, around 3 % of the study subjects mentioned a feeling of being intoxicated or drunk along with a euphoric mood. At the highest dose, subjects informed about feeling frunk, a state of euphoria, unable to pay attention, a confused state of mind, and sedation.

Drug Dependance Possibility:

Drug dependency refers to the state of developing a tendency and adaptation to regular and repeated administration of a particular drug. The clinical manifestation includes withdrawal symptoms in case the drug is abruptly discontinued.

Mentioned below are the signs and symptoms of drug dependence with Cenobamate.

• Tremor.

• Amnesia.

• Loss of appetite.

• Insomnia.

• Depression.

What Happens During an Overdose of Cenobamate?

There has not been much study done on the ill effects of an overdose of Cenobamate. Due to the same reason, there is no antidote present for Cenobamate. Thus, the standard medical protocol must be followed for the management of Cenobamate overdosage. In addition to the same, a legal poison center must be immediately contacted.

Mentioned below are the vital signs to be monitored during the management of an overdose of Cenobamate.

• Adequate and clear airway.

• Proper ventilation.

• Continuous oxygenation.

• Monitoring the cardiac rate.

• Maintaining the cardiovascular rhythm of the heart.

What Is the Chemical Structure of Cenobamate?

Cenobamate is the chemical name of the drug and is composed of carbamate. The molecular formula of carbamate is C10H10CIN5O2. The molecular weight of carbamate is 267.67 g/mol. Carbamate is an off-white crystalline powder that is highly soluble in an aqueous solution of water as well as organic solvents such as ethanol. Cenobamate is strictly for oral administration.

Mentioned below are the inactive components of Cenobamate.

• Magnesium stearate.

• Colloidal silicon dioxide.

• Microcrystalline cellulose.

• Lactose monohydrate.

• Sodium starch glycolate.

• Film coating agent.

The several kinds of film coating agents of Cenobamate are mentioned below.

• FD&C Blue# 2/indigo carmine aluminum lake.

• Iron oxide yellow.

• Iron oxide red.

• Polyethylene glycol 3350.

• Talc.

• Polyvinyl alcohol-part hydrolyzed.

• Titanium dioxide.

What Is the Mechanism of Action of Cenobamate?

The exact mechanism of action of Cenobamate is not clear as of today. There are several studies that are ongoing in order to get to the root cause of the effects caused by Cenobamate in the human body. As of today, it is known that Cenobamate has a positive therapeutic effect in patients suffering from partial-onset seizures. In addition to this, Cenobamate has been demonstrated to decrease the repetitive firing of the neuronal synapses by reducing the sodium current which is voltage-gated. Cenobamate is a positive allosteric modulator of the gamma-aminobutyric acid or GABAA ion routes.

Pharmacodynamics:

There has been no significant alteration in the attention span, memory lag, or psychomotor performance in subjects under Cenobamate treatment. There has been a significant shortening of the QT interval in candidates. It should be noted that the shortening of Qt interval was not below 300 msec.

Pharmacokinetics:

It has been established that the pharmacokinetics of Cenobamate is parallel to the pharmacokinetics of a monotherapy treatment for patients suffering from partial-onset seizures.

Mentioned below are the pharmacokinetic aspects of Cenobamate.

• The effect of Cenobamate increases as the dosage of the drug is increased.

• The attainment of a steady state of plasma concentration is achieved after roughly two weeks of dose when the drug is administered once a day.

• It should be noted that the Cmax or plasma multiple-dose exposure of Cenobamate decreases along with the administration of drugs such as Phenytoin by approximately 28 %.

• Cenobamate is 88 % absorbed after an oral route of administration.

• The median Tmax ranges from one to four hours.

• There has not been any significant alteration in the pharmacokinetics after a heavy meal or a meal rich in oil and cholesterol.

• Approximately fifty liters of Cenobamate is distributed post an oral administration of Cenobamate.

• 60 % of Cenobamate gets bind to the plasma protein which is not dependent on in vitro concentration.

• Cenobamate binds with human albumin protein before attachment to any other biological protein.

• The half-life of Cenobamate is around sixty hours.

• 0.5 liters to 0.6 liters is the roughly equivalent oral clearance of a dose ranging between 100 mg/day and 400 mg/day.

• The metabolism of Cenobamate is highly extensive and the metabolic pathway is initially by glucuronidation through the UGT2B7 as well as the UGT2B4.

• The secondary means of Cenabomate metabolism is through oxidation via the CYP2E1, CYP2A6, and CYP2B6 in addition to CYP2C19 and CYP3A4/5.

• After the administration of Cenobamate that was radiolabeled, 98 % of the drug remained unchanged in the plasma out of which 6.8 % of the dosage was excreted in the urine.

• Out of the complete radioactive dose, approximately 88 % was found in urine as against the 5.2 % which was found in feces matter.

• Within the initial seventy-two hours of dose administration, roughly 50 % of the drug was excreted.

• As compared to healthy subjects, the plasma of Cenobamate in patients suffering from mild to moderate renal impairment was approximately 1.5 folds overhead.

• Subjects with a severe nature of renal impairment did not display much change in the plasma concentration of Cenobamate.

• There have not been any studies or clinical trials on the pharmacokinetics of Cenobamate during hemodialysis.

• Subjects suffering from a mild to moderate nature of hepatic impairment presented with a 2.3-fold increase in the plasma concentration of Cenobamate.

• The intake of alcohol does not pose any significant changes in the pharmacokinetics of Cenobamate.

• When administered along with Cenobamate, no changes in the pharmacokinetics were observed in the drugs- Levetiracetam, Lacosamide, and Valproic Acid.

• The concentration and effectiveness of Lamotrigine were seen to be dropped by approximately 21 % to 52 % when used concomitant with Cenobamate.

• There has not been any clear-cut establishment of the relationship and effectiveness of Oxcarbazepine when used along with Cenobamate.

What Are the Nonclinical Toxicology Aspects of Cenobamate?

When the nonclinical toxicology of a drug is studied, carcinogenesis, mutagenesis, and fertility are the main aspects that require focus.

• Carcinogenesis:

There has not been any development of tumors in lab rats after an oral route of administration of Cenobamate. The administration was continued for up to ninety weeks.

• Mutagenesis:

Cenobamate was observed to be negative in in vitro studies for any kind of genotoxicity as well as in any in vivo micronucleus assays.

• Impairment of fertility:

There was no significant change or negative effects in the fertility cycle of lab rats of both genders after they were administered with Cenobamate prior to mating.

What Are the Aspects of Cenobamate That Require Patient Counseling?

The patients must be advised to go through the medication guide approved by the FDA beforehand. Mentioned below are the several aspects of Cenobamate that require patient counseling.

• Patients and caregivers must be explained the phenomenon of DRESS or Drug Reaction with Eosinophilia and Systemic Symptoms which is a kind of multi-organ hypersensitivity reaction. Fever, rash, hepatic dysfunction, lymphadenopathy, and other clinical manifestation as of those mentioned above must be noted down and forwarded to the respective health care provider immediately.

• Patients are requested to inform the healthcare provider about all the medications especially cardiovascular conditions as well as any herbal medicaments. Loss of consciousness, palpitations, and dizziness are a few of the signs and symptoms of short QT syndrome.

• Patients undergoing therapy with Cenobamate may show suicidal tendencies and worsen depression. The patient’s family or the respective healthcare provider is requested to keep an eye for any abnormal behavior or altered mental state of the patient.

• Imbalance while walking, fatigue and somnolence are some of the neurological adverse effects of Cenobamate that need to be addressed by the healthcare professional if observed.

• Heavy machinery must not be allowed to use by the patient undergoing therapy with Cenobamate due to insufficiency of gait.

• Alcohol and central nervous system depressants may pose an additive change in patients under treatment with Cenobamate.

• Patients must not abruptly discontinue the dosage of Cenobamate without any consultation with their respective healthcare providers.

• Cenobamate has the potential to reduce the effectiveness of contraceptives and birth control and thus patients must be duly informed regarding the same.

• Patients are requested to inform their health care provider in case they are pregnant or plan to conceive in the coming days which may clash with the treatment of Cenobamate.

• Cenobamate can be ingested with or without food but must be swallowed as a whole instead of being crushed or chewed.

Cenobamate for Patients

Cenobamate is a drug that has been approved for the treatment of adult patients suffering from partial-onset seizures.

What Is Cenobamate?

Cenobamate is a medicine that is prescribed to patients who are suffering from partial-onset seizures in adult patients. Cenobamate does not have any established safety and effectiveness in children.

Cenobamate must not be administered in the below-mentioned cases.

• There is a known allergy to any of the inactive ingredients of the drug.

• There is a familial disorder called short QT syndrome that alters the electrical impulse generation of the heart.

What Are the Side Effects of Cenobamate?

• Allergic reactions.

• Organ dysfunction.

• Abnormal blood cell count.

• Liver impairment.

• Rashes.

• Fever.

• Swelling of the tongue, eyes, lips, and face.

• Sores in the mucous membranes of the oral cavity.

• Scabs around the corners of the eyes.

• Difficulty in breathing.

• Trouble while swallowing.

• Yellow discoloration of the skin.

• Unusual bleeding.

• Bruising of the skin.

• Muscle ache.

• Weakness.

• Sore throat.

• Swollen lymph nodes.

• Discoloration of the sclera of the eye.

• Hives.

• Fatigue.

• Suicidal actions or thoughts.

• Trouble while sleeping.

• Feeling to end one’s life.

• Several attempts of suicide.

• Irritability.

• Worsening of depression.

• Increased state of anger.

• Aggressiveness.

• Violent behavior.

• Anxiety.

• Restlessness.

• Altered electrical impulses.

• Episodes of panic attacks.

• Increase frequency of speaking.

• Manic attacks.

• Mood swings.

• A drastic change in one’s behavior.

• Unable to process thoughts.

• Not able to focus and concentrate.

• Memory impairment.

• Disruptive ability to think straight.

• Double vision.

Can Treatment With Cenobamate Be Stopped?

• Cenobamate must be administered only after consultation and prescription by a health care provider.

• Cenobamate must not be abruptly stopped since it may lead to serious complications.

• Seizure episodes may be returned in case Cenobamate is abruptly stopped.

Is Drug Abuse Possible With Cenobamate?

Cenobamate is a controlled drug that is currently pending a decision from DEA since it has the potential to be abused as well as turn the patient dependent on the particular drug. For these reasons, Cenobamate must be kept in a safe place, away from the reach of children.

What Are the Medical Conditions That Must Be Informed to the Healthcare Provider Before Treatment With Cenobamate?

The patient is expected to mention the below medical conditions before going ahead with the treatment of Cenobamate.

• Depression.

• Mood swings.

• Suicidal actions.

• Liver impairment.

• Kidney disfunction.

• Alterations in blood components.

• Anaphylactic reactions.

• Underlying medical conditions of internal organs.

• Intake of birth control medications.

• Pregnancy and lactation.

• Over-the-counter drugs.

• Herbal supplements.

• Multivitamins and minerals.

What Activities Should Be Avoided While Under Treatment With Cenobamate?

• Do not consume alcohol.

• Do not drive after eating Cenobamate.

• Do not use heavy machinery when under the influence of Cenobamate.

• Do not perform activities that require motor and visual focus.