Oxcarbazepine - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Oxcarbazepine is a medication used alone or in combination with drugs to treat partial seizures. It is available as an oral tablet and an oral suspension. It acts by inhibiting the sodium channels, thereby preventing the high-frequency firing in the neurons responsible for seizure episodes. The United State Food and Drug Administration (FDA) approved Oxcarbazepine for the treatment of seizures in 1999. The off-label indications of the drug include maintenance of neuropathy due to diabetes mellitus and treatment of trigeminal neuralgia.

The drug has been reported to cause myelosuppression (suppression of the bone marrow to make sufficient blood cells) and hyponatremia (low sodium levels) in some patients. While taking this medication, check for symptoms like extreme paleness, fatigue, shortness of breath, seizures, restlessness, and severe headache, and seek immediate professional help for the required medical intervention. Alcohol use should be limited while taking Oxcarbazepine due to the potential risk of additive sedation.

How Does Oxcarbazepine Work?

Oxcarbazepine is classified under the group of medications called anticonvulsants. It decreases the frequency of multiple firing in neurons, thus eliciting a calming effect by decreasing the irregular electrical activity in the brain's nerve cells.

Dosage:

• Oxcarbazepine is available as 150 mg, 300 mg, 600 mg immediate-release, and extended-release tablets.

• For seizures, the initial dosing of Oxcarbazepine is 600 mg/day on an empty stomach (one hour before or two hours after food) for extended-release tablets and starting with 300 mg/day for immediate-release tablets.

• The physician will adjust the dose based on the response to the treatment after the start of the therapy.

• Patients are advised to limit the use of alcohol as it may increase sedation for immediate-release tablets.

• In case of any queries or doubts, contact the doctor or pharmacist promptly.

What Are the Drug Warnings for Oxcarbazepine?

• Hyponatremia: Oxcarbazepine may cause a decline in the sodium levels in the blood. The symptoms include headache, seizures, fainting, etc. These symptoms should be immediately brought to the physician's notice for the necessary treatment.

• Dermatological Reactions: Oxcarbazepine can lead to serious skin reactions like Steven-Johnsons syndrome, which can be life-threatening. The drug may be discontinued if the symptoms recur on re-administration.

• Mood Changes: Oxcarbazepine can worsen various psychiatric conditions like anxiety and depression and cause rapid behavior changes.

• Risk of Aggravation of Seizures: Oxcarbazepine may lead to worsening seizures in some individuals. This should be reported to the doctor at the earliest.

• Pregnancy: Talk to the doctor if the patient is pregnant or intends to get pregnant before taking the medication.

For Patients:

What Is Partial Seizure?

Seizures are a sudden surge of electrical activity in the brain. It can cause convulsions, loss of consciousness, and muscle spasms. The most common type of seizure is a partial (focal) seizure, which can affect one or more areas on either side of the brain. Partial seizures can be focal aware or focal impaired, depending on whether the person experiencing it knows what is happening during their seizure or not. Partial seizures are usually short in duration and may cause physical symptoms such as twitching, shaking, jerking, loss of awareness, or speech difficulties.

The causes and symptoms vary depending on which area(s) of the seizure affects the brain. For example, if an epileptic has right temporal lobe epilepsy may experience hallucinations and other psychotic symptoms such as paranoia. If an epileptic has left temporal lobe epilepsy, they may experience language problems and difficulty with memory retention. Treatment for seizures is different for everyone depending on the cause and severity. If a seizure is not treated properly, it can lead to serious health problems like coma or death.

Learn More About Oxcarbazepine:

Before Starting Oxcarbazepine:

When and Why to Take Oxcarbazepine?

Oxcarbazepine is a prescription medication used to control seizures. It should be taken as per the doctor's order.

What are the Things to Inform The Doctor Before Taking Prescribe Oxcarbazepine?

Inform the doctor if any of the following conditions are present:

• Previous history of allergy to any drug or components of the medication.

• If the patient has any liver diseases, the doses need to be adjusted.

• Have kidney diseases which are particularly associated with reduced levels of sodium in the blood.

• Taking any medications that can lower the sodium levels in the body, like Desmopressin, Indomethacin, Ibuprofen, or drugs belonging to the diuretic class.

• Have heart diseases like heart failure, changes in heart rhythm, or if the patient experiences breathlessness or swollen legs.

• Oxcarbazepine can also result in a decrease in thyroid levels in some patients. Check the thyroid levels regularly, especially in children.

• If the patient is using hormonal contraceptives.

Starting Oxcarbazepine:

How Is Oxcarbazepine Given?

The starting dose is 300 mg daily for immediate-release tablets and 600 mg for extended-release tablets. The doctor may adjust the dose if any other anticonvulsant drug is given. Follow the instructions carefully. The extended-release tablets should be taken on an empty stomach.

Things to Do After Starting Oxcarbazepine:

Oxcarbazepine administered can result in side effects. It is important to follow up with the doctor to assess the progress of the treatment and to see if any side effects are experienced. If the frequency of the seizures is reduced, the doctor must be notified to make the necessary changes in the drug dose.

What Are the Side Effects of Oxcarbazepine?

The side effects of Oxcarbazepine include:

Common:

• Tiredness.

• Shortness of breath, especially during physical activity.

• Headache.

• Chills.

• Infections leading to fever.

• Dizziness.

• Easy bruising or bleeding.

• Sore throat.

• Mouth ulcer.

• Reddish or purplish patches and unexplained blotches on the skin.

The more severe side effects of the medication include:

• Severe mood changes and self-harming ideation in some individuals.

• Life-threatening conditions like Steven Johnson's syndrome or toxic epidermal necrolysis are presented with extreme rash or discolored scars on the skin, ulcers in the nose, mouth, and genitals, and blistering the skin.

• Oxcarbazepine can also result in a decrease in thyroid levels in some patients.

• Decrease in thyroid levels.

Dietary Alterations:

Follow the dietary changes as advised by the doctor or dietician. Avoid the consumption of alcohol-containing food or beverages while taking this medication. Some formulations of Oxcarbazepine contain lactose as an inactive ingredient. Patients with lactose intolerance should inform the doctor before taking the medication. If the patient is taking medications for other conditions, inform the doctor of all the prescriptions, non-prescription, and supplements before taking the medication. Follow the instructions as advised.

What Should Be Done if a Dose Is Missed?

If a dose is missed, take it as soon as it is remembered and continue with the normal dosing regimen. However, if it is almost time for the next dose, skip the previous one and continue as scheduled. Avoid taking double doses to make up for a missed dose. In case of queries, contact the pharmacist or the doctor.

What Should Be Done to Treat Oxcarbazepine Overdose?

Avoid taking the tablet more than the advised dosage. Only take the number of tablets the doctor specified on the pharmacy label. Inform the doctor immediately if an overdose happens, or visit the local accident and emergency department.

How to Store Oxcarbazepine?

• Store Oxcarbazepine tablets at room temperature between 15 to 30 degrees Celsius.

• Keep the tablets away from children and pets.

• The disposal of medications in wastewater or household waste is not recommended. Check how to dispose of expired medicines, according to a pharmacist. These actions will aid in keeping the environment safe.

Avoid Self-Medication:

Avoid taking this drug without a prescription, do not recommend it to others, and do not take it on someone else's advice. Different people react to medications differently, and some may even react worse. Make a list of all the prescriptions and non-prescription that are being taken whenever consulting a doctor, and take the medication only as instructed by a qualified healthcare professional.

For Doctors

Indication:

Oxcarbazepine is indicated in the following conditions:

Adults:

The use of adjuvant therapy or monotherapy to treat partial seizures.

Pediatrics:

• The use of monotherapy to treat partial seizures in children aged four to 16 years.

• The use of adjunctive therapy to treat partial seizures in children aged two to 16 years.

Adult Dosing:

Monotherapy for Partial Seizure:

• For Extended-Release Tablet: Starting with a dose of 600 mg/day orally once daily for one week on an empty stomach. The dose may be increased by 600 mg, bringing the total daily dose to between 1200 and 2400 mg.

• For Immediate-Release Tablet or Suspension: Starting with a dose of 300 mg orally twice a day; may raise the dose to 1200 mg/day by adding 300 mg/day every third day.

• Conversion to Monotherapy Immediate-Release Tablet or Suspension: Starting with 300 mg orally twice a day; may increase the doses by up to 600 mg/day at weekly intervals to a maximum dose of 2400 mg/day reached in about two to four weeks while simultaneously reducing the dosage of concomitant antiepileptic drug over three to six weeks.

Adjunct Partial Seizure:

• Extended-Release Tablet: Starting with a dose of 600 mg/day orally once daily for one week on an empty stomach. The dose may be increased by 600 mg, bringing the total daily dose to between 1200 and 2400 mg.

• Immediate-Release Tablet or Suspension: Starting with 300 mg orally twice a day; the dose may be increased weekly by up to 600 mg/day to a maximum of 1200 mg/day.

Other Dosing Considerations:

For Extended-Release Tablets:

Renal Impairment (Creatinine Clearance (CrCl) less than 30 mL/min):

• Starting with a dose of 300 mg/day, up to 450 mg/day may be added in weekly increments.

• In renal impairment (dialysis-dependent end-stage renal disease), the extended-release Oxcarbazepine is replaced with immediate-release.

• Avoid use in severe hepatic dysfunction.

• In geriatric patients, the initial dose is 300 mg or 450 mg; doses may be increased monthly from 300 mg to 450 mg.

• When using potent CYP3A4 inducers concurrently with Oxcarbazepine extended-release, it is recommended to start with 900 mg orally once daily for adults and 12 to 15 mg/kg orally once daily (not to exceed 900 mg per day in the first week) for pediatric patients. Dosage adjustment may be necessary after initiating, modifying, or stopping inducers.

Immediate-Release Tablets:

Renal Impairment (CrCl less than 30 mL/min):

• 150 mg/day given twice daily and increased slowly to achieve the desired clinical response.

Pharmacology

Mechanism of Action:

The exact mechanism by which Oxcarbazepine exerts its anticonvulsant effect is unknown. It is known that the pharmacological activity of Oxcarbazepine occurs primarily through its 10-monohydroxy metabolite (MHD). Studies conducted in vitro show that MHD causes the blocking of voltage-sensitive sodium channels, stabilizes hyper-excited neuronal membranes, prevents recurrent neuronal discharges, and slows synaptic impulse propagation.

Pharmacodynamics:

Oxcarbazepine and its active metabolite have anticonvulsant effects in animal seizure models. They eliminated or significantly decreased the incidence of continuously recurring focal seizures in Rhesus monkeys with aluminum implants, as well as provided protection against electrically generated tonic extension seizures in rodents and, to a lesser extent, chemically induced clonic seizures.

Absorption:

Patients receiving twice-daily Oxcarbazepine reach steady-state plasma concentrations of MHD in two to three days. Over the dose range of 300 to 2400 mg/day, the pharmacokinetics of MHD are linear and exhibit dose proportionality at a steady state.

Distribution:

MHD is mostly linked to albumin in serum proteins, where it occupies a 40 % binding capacity. Within the therapeutically relevant range, binding is not reliant on serum concentration. Alpha-1-acid glycoprotein is not bindable to Oxcarbazepine or MHD. It has a volume of distribution of 49 L.

Metabolism:

Cytosolic enzymes primarily reduce Oxcarbazepine into its active metabolite. It is then further metabolized by glucuronic acid conjugation.

Excretion:

Oxcarbazepine is excreted as metabolites that are primarily eliminated by the kidneys. Less than one percent of the dose is found as unaltered Oxcarbazepine, with more than 95 % of the dose excreted in the urine. Less than four percent of the dosage given is excreted in the feces.

Toxicity:

Non-Clinical Toxicology:

• Carcinogenesis: Rats exposed to 250 mg/kg/day of Oxcarbazepine and 250 mg/kg/day of MHD saw an increase in the incidence of benign testicular interstitial cell tumors, whereas rats exposed to 600 mg/kg/day of MHD experienced an increase in the incidence of granular cell tumors in the cervix and vagina.

• Mutagenicity: No mutagenic effects were observed in animal studies of Oxcarbazepine.

• Impairment in Fertility: In a fertility trial, rats were given MHD (50, 150, or 450 mg/kg) orally before and during mating and early gestation. The highest dose interrupted estrous cyclicity and decreased the number of corpora lutea, implantations, and viable embryos in the females.

Clinical Toxicity:

• Management of Mild to Moderate Toxicity: Supportive and symptomatic care is provided. Use IV (intravenous) fluids to treat mild hypotension. Use 0.9 % sodium chloride and water restriction to treat mild hyponatremia.

• Management of Severe Toxicity: Supportive and symptomatic care are provided. Administer IV fluids, Dopamine, or Norepinephrine to treat severe hypotension. Use IV benzodiazepines to treat seizures; barbiturates or Propofol may be required if they last or recur. Oxygen therapy, bronchodilators, Diphenhydramine, corticosteroids, vasopressors, and Epinephrine, may be necessary for patients who are experiencing an acute allergic reaction. Use 0.9 % sodium chloride to treat severe hyponatremia; 3 % sodium chloride may be used for extremely symptomatic hyponatremia.

Warnings and Precautions:

• Beers Criteria: When taken for epilepsy or mood disorders, older persons with a history of falls or fractures should avoid using it because it may result in syncope, reduced psychomotor function, or ataxia. Avoid using three or more CNS-active medications simultaneously in any combination due to the increased risk of falling. Use caution if prescribed since SIADH (syndrome of inappropriate antidiuretic hormone secretion) or hyponatremia could develop or worsen; keep an eye on the sodium levels when starting or changing doses.

• Dermatologic Reactions: If severe dermatological reactions occur (including Stevens-Johnson syndrome and toxic epidermal necrolysis), which could be fatal or life-threatening. Test at-risk patients for HLA-B*1502 and, if present, avoid use unless benefits clearly outweigh risks. Patients with the HLA-B*1502 (most prevalent in Chinese, Thai, Filipino, Malaysian, Korean, and eastern Indian populations) have an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis.

• Metabolic Changes: Monitoring is advised. Clinically severe hyponatremia (sodium less than 120 mmol/L) and SIADH (syndrome of inappropriate antidiuretic hormone secretion) may occur, particularly during the first three months of medication and more than one year after therapy commencement. T4 levels might drop without corresponding T3 or TSH drops. Dose interruption or withdrawal may be required.

• Hematologic: If hematological reactions, including pancytopenia, agranulocytosis, and leukopenia, have been reported, discontinue use.

• Hepatic: Patients with severe hepatic impairment should not use extended-release tablets, and immediate-release forms should be used with care.

• Hypersensitivity: Increased risk of hypersensitivity reaction in patients who have previously had hypersensitivity to Carbamazepine (about 25 % to 30 % will do so with Oxcarbazepine); use only if the potential benefit outweighs the risk; stop using immediately if hypersensitivity signs or symptoms appear. Drug responses with eosinophilia and systemic symptoms (DRESS) or multiorgan hypersensitivity reactions have happened; if this has happened, stop using the drug immediately. There have been fatal cases of angioedema and anaphylaxis of the larynx, glottis, lips, and eyelids; urgent and permanent withdrawal is advised in such cases.

• Neurologic: Adverse cognitive and neuropsychiatric events, such as psychomotor retardation, concentration problems, speech or language issues, sleepiness or weariness, or atypical coordination (such as ataxia and gait impairments), have been observed; monitoring is advised. Quick discontinuation may be considered if the withdrawal is required owing to a major adverse event. Avoid rapid withdrawal, as this may increase seizure frequency and the risk of status epilepticus. It has been observed that primary generalized seizures can develop suddenly or worsen; if this happens, stop taking the medication.

• Reproductive: Non-hormonal forms of contraception are advised because therapy may reduce the effectiveness of hormonal contraceptives (extended-release).

Contraindications:

Oxcarbazepine is contraindicated in patients with:

• A history of hypersensitivity to the drug or its components.

• Concurrent administration with drugs Cabotegravir, Doravirine, and Rilpivirine.

Clinical Studies:

Studies have shown that Oxcarbazepine monotherapy is just as effective at reducing the frequency of generalized tonic-clonic and partial seizures in newly diagnosed adult patients as Phenytoin plus Valproic acid. Oxcarbazepine 2400 mg/day, used as monotherapy, has shown promise in treating adult patients with refractory partial seizures. In 692 individuals with refractory partial seizures, Oxcarbazepine 600, 1200, and 2400 mg/day as an additional therapy significantly decreased seizure frequency compared with a placebo. The effectiveness of Oxcarbazepine monotherapy in treating children and adolescents with newly diagnosed partial or generalized tonic-clonic seizures is comparable to that of Phenytoin.

Drug Interactions:

The drug interactions of Oxcarbazepine are as listed:

1. With Other Drugs:

• Alfentanil.

• Amiodarone.

• Belzutifan.

• Benzhydrocodone.

• Buprenorphine.

• Calcifediol.

• Carbamazepine.

• Cilostazol.

• Citalopram.

• Clarithromycin.

• Cobicistat.

• Codeine.

• Daclatasvir.

• Darunavir.

• Desogestrel.

• Dienogest.

• Dihydrocodeine.

• Dolutegravir.

• Doxorubicin.

• Dronedarone.

• Drospirenone.

• Elvitegravir.

• Enzalutamide.

• Estradiol.

• Ethinyl Estradiol.

• Ethynodiol.

• Etonogestrel.

• Fentanyl.

• Fexinidazole.

• Fosphenytoin.

• Gestodene.

• Hemin.

• Hydrocodone.

• Ifosfamide.

• Lacosamide.

• Ledipasvir.

• Levonorgestrel.

• Linagliptin.

• Lumacaftor.

• Lumateperone.

• Mavacamten.

• Medroxyprogesterone.

• Meperidine.

• Mestranol.

• Methadone.

• Mitotane.

• Naloxegol.

• Nifedipine.

• Nomegestrol.

• Norelgestromin.

• Norethindrone.

• Norgestimate.

• Norgestrel.

• Orlistat.

• Oxycodone.

• Paclitaxel.

• Palbociclib.

• Panobinostat.

• Pentazocine.

• Perampanel.

• Phenobarbital.

• Phenytoin.

• Rifampin.

• Rivaroxaban.

• Segesterone.

• Sertraline.

• Simeprevir.

• St John's Wort.

• Sufentanil.

• Tacrolimus.

• Tenofovir Alafenamide.

• Tolvaptan.

• Tramadol.

• Tranylcypromine.

• Ubrogepant.

• Ulipristal.

• Velpatasvir.

• Vilazodone.

• Voxilaprevir.

• Felodipine.

• Ginkgo.

• Lamotrigine.

• Ospemifene.

• Simvastatin.

• Valproic Acid.

• Verapamil.

2. With Alcohol: Alcohol can attenuate the neurological side effects of Oxcarbazepine.

3. With Food: No specific food-drug interactions are reported for Oxcarbazepine.

Other Specifications:

• Oxcarbazepine in Pregnant Women: Monitoring is advised both during pregnancy and after delivery since plasma concentrations of the active metabolite of Oxcarbazepine may progressively rise during pregnancy and fall after delivery.

• Oxcarbazepine in Lactating Women: Oxcarbazepine passes through breast milk. Given the possibility of major side effects from Oxcarbazepine in nursing infants, a choice should be made on whether to stop breastfeeding or to stop the medication in nursing mothers, taking into account the significance of the medication to the mother.

• Oxcarbazepine in Pediatric Patients: Oxcarbazepine is approved for use as adjunctive therapy in patients two to 16 years old who are experiencing partial seizures. It has not been demonstrated whether using it as adjuvant therapy for children patients under the age of two is safe or effective. For patients aged four to 16 who are experiencing partial seizures, Oxcarbazepine is also recommended as a monotherapy. In children under the age of four, the effectiveness and safety of using a single medication to treat partial seizures have not been established.

• Oxcarbazepine in Geriatric Patients: Monitoring is required in geriatric patients presented with hyponatremia.

• Oxcarbazepine in Patients With Renal Impairment: Dosing adjustment is required as indicated in special consideration for the dosing of Oxcarbazepine.

• Oxcarbazepine in Patients With Hepatic Impairment: No dosing adjustment is required for patients with mild to moderate hepatic impairment. However, avoid use in cases of severe hepatic impairment.