oxcarbazepine

Oxcarbazepine is an anticonvulsant used in the treatment of partial (focal) onset seizures in both adults and pediatric epileptic patients.

Seizures are caused by abnormal electrical activity in the brain and partial or focal seizure is a type of seizure in which the abnormal electrical activity is confined to a limited area of the brain. Oxcarbazepine may also be used to treat bipolar disorder and nerve pain (neuralgia) and nerve damage (neuropathy) that result from certain neurological diseases.

Oxcarbazepine reduces the incidence and frequency of seizure and prevents its spread by inhibiting abnormal electrical activity in the brain. Oxcarbazepine and its active metabolite 10-monohydroxy derivative (MHD) work by blocking the voltage-sensitive sodium channels, stabilizing the nerve cell membranes and reducing their excitability. This inhibits repetitive neuronal firing and propagation of nerve impulses to other parts of the brain. Oxcarbazepine also enhances potassium conductance and modulates the activity of calcium channels.

The immediate release formulation of oxcarbazepine is approved by the FDA for use as monotherapy in adults and children 4 to 16 years of age and as adjunctive therapy in children 2 to 16 years of age. The extended-release formulation is approved to treat patients 6 years and older. Other off-label uses of oxcarbazepine in adults include:

4 off-label uses for oxcarbazepine

• Trigeminal neuralgia
• Bipolar disorder
• Neuralgia/neuropathy
• Diabetic neuropathy

• Do not use oxcarbazepine in patients with known hypersensitivity to oxcarbazepine, any of the components in the formulation, or to eslicarbazepine acetate.
• Oxcarbazepine is similar in structure to carbamazepine, another anticonvulsant drug. Patients hypersensitive to carbamazepine are likely to have cross sensitivity to oxcarbazepine, exercise caution.
• Hypersensitivity symptoms may include angioedema and anaphylaxis, which can be fatal. Discontinue oxcarbazepine immediately if the patient develops signs of hypersensitivity.
• Oxcarbazepine may cause serious, life-threatening dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). People carrying HLA-B 1502 allele are at a higher risk for SJS and TEN. If the patient develops skin reactions, discontinue oxcarbazepine and consider alternate therapy.
• Oxcarbazepine therapy may cause sodium levels to drop and lead to hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Monitor patient’s sodium levels, especially if the patient is receiving other medications known to decrease sodium levels.
• Antiepileptic drugs including oxcarbazepine can increase the risk of suicidal thoughts and behavior. Patients, their families, and caregivers should be appropriately cautioned.
• Oxcarbazepine should be withdrawn gradually because abrupt discontinuation may increase seizure frequency or precipitate status epilepticus, a state of prolonged seizure lasting longer than 5 minutes.
• Oxcarbazepine may impair cognitive and motor skills, and cause drowsiness and fatigue. Patients should be cautioned to avoid hazardous activities until the effects of the drug can be determined.
• Oxcarbazepine can cause drug reactions with eosinophilia and systemic symptoms (DRESS), also known as multi-organ hypersensitivity, which can be life-threatening or fatal. If the patient develops fever, rash, facial and/or lymph node swelling, assess the patient and discontinue the drug immediately if alternate reasons for the symptoms cannot be established.
• There are rare reports of blood disorders that include reduced counts of all types of blood cells. Monitor patient for symptoms.
• Oxcarbazepine’s active metabolite 10-monohydroxy derivative (MHD) may gradually decrease throughout pregnancy, due to physiological changes. Monitor patients closely during pregnancy and through the postpartum period because MHD levels may return after delivery.
• Concurrent use of oxcarbazepine with hormonal contraceptives may reduce the contraceptive efficacy, caution patients.
• There are reports of exacerbation or new onset of primary generalized seizures with oxcarbazepine treatment, particularly in children, although it may occur in adults as well. Discontinue the drug if seizures are aggravated.
• There are reports of hypothyroidism, with thyroxine levels returning to normal after discontinuation of oxcarbazepine. Monitor thyroid function, especially in children.
• Patients with impaired kidney function may require dose adjustment.
• Standard and extended-release oxcarbazepine formulations (Trileptal and Oxtellar XR) are not bioequivalent and not interchangeable on mg-per-mg basis.
• Some formulations may contain propylene glycol, which can be toxic in large amounts, particularly in newborn babies. Use with caution.

Common side effects of oxcarbazepine include:

• Drowsiness (somnolence)
• Dizziness
• Impaired coordination, balance and speech (ataxia)
• Abnormal gait
• Tremor
• Fatigue
• Headache
• Vertigo
• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Constipation
• Indigestion (dyspepsia)
• Gastritis
• Loss of appetite (anorexia)
• Dry mouth
• Rectal hemorrhage
• Toothache
• Low sodium levels in blood (hyponatremia)
• Thirst
• Double vision (diplopia)
• Abnormal vision
• Repetitive uncontrolled eye movements (nystagmus)
• Abnormal eye focusing (accommodation)
• Taste perversion
• Ear ache
• Ear infection
• Acne
• Rash
• Flat, red, and raised lesions (maculopapular rash)
• Bruising and purple spots (purpura)
• Hot flushes
• Increased sweating
• Reduced skin sensation (hypoesthesia)
• Insomnia
• Abnormal thinking
• Agitation
• Nervousness
• Confusion
• Difficulty concentrating
• Memory loss (amnesia)
• Mood swings (emotional lability)
• Aggravated convulsions
• Involuntary muscle contractions
• Abnormal EEG
• Cranial injury
• Muscle weakness
• Sprains and strains
• Back pain
• Falling down
• Fever
• Weakness (asthenia)
• Feeling abnormal
• Leg swelling (edema)
• Generalized edema
• Increase in weight
• Allergy
• Chest pain
• Low blood pressure (hypotension)
• Upper respiratory tract infection
• Pneumonia
• Coughing
• Nosebleed (epistaxis)
• Nasal inflammation (rhinitis)
• Sinus inflammation (sinusitis)
• Throat inflammation (pharyngitis)
• Bronchial inflammation (bronchitis)
• Infection
• Viral infection
• Chest infection
• Lymph node swelling (lymphadenopathy)
• Urinary tract infection
• Urinary frequency
• Vaginal inflammation (vaginitis)

Serious side effects of oxcarbazepine include:

• Swelling of tissue under the skin and mucous membranes (angioedema)
• Severe allergic reaction (anaphylaxis)
• Serious skin reactions including:
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
• Suicidal behavior and ideation
• Increase in seizure frequency (with discontinuation)
• Status epilepticus, a state of prolonged seizure (with discontinuation)
• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Bone marrow suppression
• Blood disorders including:
  • Low count of leukocyte immune cells (leukopenia)
  • Low count of granulocyte immune cells (agranulocytosis)
  • Low count of all types of blood cells (pancytopenia)
  • Low red blood cell count due to lack of production (aplastic anemia)
  • Low platelet count (thrombocytopenia)

Less common side effects of oxcarbazepine include:

• Palpitation
• Slow or rapid heart rate (bradycardia or tachycardia)
• Cardiac failure
• Fainting (syncope)
• Cerebral hemorrhage
• Low or high blood sugar (hypoglycemia/hyperglycemia)
• Low calcium (hypocalcemia)
• Low potassium (hypokalemia)
• Elevated liver enzymes
• Asthma
• Shortness of breath (dyspnea)
• Inflammation of lung’s lining (pleurisy)
• Drug-related movement disorders (extrapyramidal disorder)
• Migraine
• Ringing in ears (tinnitus)
• Delirium
• Delusions
• Psychosis
• Changes in libido
• Painful and prolonged erection (priapism)
• Painful urination (dysuria)
• Blood in urine (hematuria)
• Excessive urination (polyuria)
• Kidney stone
• Intermenstrual bleeding
• Excessive menstrual bleeding (menorrhagia)
• White discharge (leukorrhea)
• Systemic lupus erythematosus

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 150 mg
• 300 mg
• 600 mg

Tablet, extended-release

• 150 mg
• 300 mg
• 600 mg

Oral suspension

• 300 mg/5 mL

Adult:

Partial Seizures

Adjunctive treatment

• Trileptal: 300 mg orally every 12 hours initially; may increase at weekly intervals by 600 mg/day up to 1200 mg/day
• Oxtellar XR: 600 mg orally every day initially; may increase at weekly intervals by 600 mg/day increments to target dosage range of 1200-2400 mg every day

Monotherapy (if converting from other AED)

• Initial: 300 mg orally every 12 hours; increase by 600 mg/day every week up to 2400 mg/day
• Reduce and withdraw concomitant antiepileptic drugs (AEDs) over 3-6 weeks while reaching maximum oxcarbazepine dose in 2-4 weeks

Monotherapy (if AED naive)

• Initial: 300 mg orally every 12 hours; increase by 300 mg/day every 3 days to 1200 mg/day divided every 12 hours

Bipolar Disorder (Off-label)

• 300 mg/day orally initially; may titrate to 1800-2400 mg/day maximum

Diabetic Neuropathy (Off-label)

• 150-300 mg/day orally initially; may increase to 900-1200 mg/day (general recommendation)
• Doses up to 1800 mg/day studied, with positive results

Neuralgia/Neuropathy (Off-label)

• 300 mg PO every 8-12 hours initially; may adjust dose to 400-2000 mg divided every 8-12 hours (maximum tolerated or effective dose)

Dosage Modifications

Strong CYP3A4 inducers or UGT inducers

• Strong CYP3A4 inducers and/or UGT inducers decrease systemic exposure to 10-monohydroxy derivative (MHD), the active metabolite
• Dosage adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of such inducers
• Oxtellar XR: Initiate at 900 mg every day

Renal impairment

• There is a linear correlation between creatinine clearance (CrCl) and the renal clearance of MHD
• Severe (CrCl less than 30 mL/minute)
  • Oxtellar XR: Administer lower starting dosage and increase, if necessary, at a slower than usual rate until the desired clinical response is achieved
  • Trileptal: Decrease usual starting dose by 50% and increase slowly to achieve desired clinical response
  • ESRD: Use immediate-release oxcarbazepine instead of long-acting

Hepatic impairment

• Mild-to-moderate: No dose adjustment required
• Severe: Not evaluated, and therefore is not recommended

Dosing Considerations

• Conversion from immediate release to Oxtellar XR: Higher doses of Oxtellar XR may be required

Geriatric:

• For extended-release dosage administration consider initial dose of 300-450 mg/day
• May increase at weekly intervals to desired effect; not to exceed 2400 mg/day

Pediatric:

Partial Seizures (Adjunctive Treatment)

Trileptal (age 2-4 years)

• Initial: 8-10 mg/kg/day orally divided every 12 hours; not to exceed 600 mg/day  
• Below 20 kg: May consider starting with 16-20 mg/kg/day; may titrate to higher dose over 2-4 weeks; not to exceed 60 mg/kg/day

Trileptal (age 4-16 years)

• Initial: 8-10 mg/kg/day orally divided every 12 hours; not to exceed 600 mg/day  
• Target maintenance dose: May titrate to higher dose over 2 weeks to reach the following dosage ranges
• 20-29 kg: 450 mg orally every 12 hours
• 29.1-39 kg: 600 mg orally every 12 hours
• Above 39 kg: 900 mg orally every 12 hours

Oxtellar XR (age 6-17 years)

• Initial: 8-10 mg/kg orally every day; not to exceed 600 mg/day in the first week  
• Target maintenance dose
  • May titrate to higher dose at weekly intervals in 8-10 mg/kg/day increments (not to exceed 600 mg) to reach the following target maintenance dosage ranges over 2-3 weeks
  • 20-29 kg: 900 mg orally every day
  • 29-39 kg: 1200 mg orally every day
  • Above 39 kg: 1800 mg orally every day

Partial Seizures (Monotherapy)

Trileptal (age 4-16 years)

• Conversion to monotherapy in patients receiving concomitant AEDs: 8-10 mg/kg/day orally divided every 12 hours initially, while simultaneously reducing concomitant AEDs dose(s) over 3-6 weeks; may increase Trileptal dose every week by maximum increment of 10 mg/kg/day  
• AED-naive: Initial 8-10 mg/kg/day orally divided every 12 hours; may increase every 3 days by 5 mg/kg/day
• Target maintenance dose
  • 20-24.99 kg: 600-900 mg/day
  • 25-34.99 kg: 900-1200 mg/day
  • 35-44.99 kg: 900-1500 mg/day
  • 45-49.99 kg: 1200-1500 mg/day
  • 50-59.99 kg: 1200-1800 mg/day
  • 60-69.99 kg: 1200-2100 mg/day
  • 70 kg: 1500-2100 mg/day

Oxtellar XR (age 6-17 years)

• Initial: 8-10 mg/kg orally every day; not to exceed 600 mg/day in the first week  
• Target maintenance dose
  • May titrate to higher dose at weekly intervals in 8-10 mg/kg/day increments (not to exceed 600 mg) to reach the following target maintenance dosage ranges over 2-3 weeks
  • 20-29 kg: 900 mg orally every day
  • 29-39 kg: 1200 mg orally every day
  • Above 39 kg: 1800 mg orally every day

Dosage Modifications

Strong CYP3A4 inducers or UGT inducers

• Strong CYP3A4 inducers and/or UGT inducers decrease systemic exposure to 10-monohydroxy derivative (MHD), the active metabolite
• Dosage adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of such inducers
• Oxtellar XR: Initiate at 12-15 mg/kg every day (not to exceed 900 mg/day in first week)

Renal impairment

• There is a linear correlation between creatinine clearance and the renal clearance of MHD (active metabolite)
• Recommendations for children with renal impairment are not available

Hepatic impairment

• Mild to moderate: No dose adjustment required
• Severe: Unknown if dosage adjustment necessary for immediate release dosage form; extended release, not recommended

Dosing Considerations

• Conversion from immediate-release to Oxtellar XR: Higher doses of Oxtellar XR may be required

• There have been isolated reports of overdose with immediate-release oxcarbazepine, with a maximum dose of approximately 48,000 mg. All overdose patients recovered with symptomatic care.
• Overdose symptoms included nausea, vomiting, drowsiness, aggression, agitation, confusion, low blood pressure, heart rhythm disturbance (QT prolongation), headache, dizziness, shortness of breath, constricted pupils, double vision, blurred vision, involuntary eye movement, tremor, impaired coordination, movement disorder, reduced urine output, convulsion and coma.
• There is no specific antidote for oxcarbazepine overdose. Treatment is symptomatic and supportive care including elimination of undigested drug by gastric lavage and administration of activated charcoal.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Oxcarbazepine has severe interactions with at least 20 different drugs.
• Oxcarbazepine has serious interactions with at least 71 different drugs.
• Oxcarbazepine has moderate interactions with at least 152 different drugs.
• Oxcarbazepine has mild interactions with at 83 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no adequate and well-controlled studies of oxcarbazepine use in pregnant women, however, oxcarbazepine is structurally related to carbamazepine, considered to cause fetal abnormalities.
• Animal studies and limited data available on use in pregnancy suggest oxcarbazepine and its active metabolite 10-hydroxy metabolite (MHD) may be associated with congenital malformations.
• Oxcarbazepine should be used during pregnancy only if maternal benefits outweigh potential risks to the fetus.
• Seizure frequency may increase during pregnancy because of altered levels of MHD. Patients should be monitored carefully during pregnancy and through the postpartum period.
• Oxcarbazepine and MHD are present in breast milk, and its effects on milk production and the breastfed infant are not known. Based on the importance of the drug to the nursing mother, the risks to the infant from exposure to the drug or the mother’s underlying condition, decision should be made to discontinue the drug or nursing.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as oxcarbazepine, during pregnancy.  Women taking oxcarbazepine during pregnancy should be encouraged to enroll in the North American Antiepileptic Drug (NAAED Pregnancy Registry) by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.

• Take oxcarbazepine exactly as prescribed. Do not interchange different brands.
• Oxcarbazepine may induce depression and suicidal thoughts. Seek support from family, friends and your healthcare provider if you feel depressed.
• If you are a family member or caregiver of a patient receiving oxcarbazepine therapy, be alert for signs and symptoms of depression and contact the healthcare provider if you notice unusual changes in the patient’s behavior.
• Contact your physician immediately if you develop any of the following conditions:
  • Skin reactions
  • Hypersensitivity reactions such as swelling of the face and/or throat
  • Fever, rash, and lymph node and/or facial swelling
  • Low sodium symptoms such as nausea, headache, lethargy, and confusion
  • Aggravation of seizures or increase in seizure frequency
• Oxcarbazepine can impair mental and physical abilities, avoid engaging in hazardous activities such as driving and operating heavy machinery until the drug effects can be determined.
• Store oxcarbazepine safely out of reach of children.
• In case of overdose, seek medical help immediately or contact Poison Control.