oxcarbazepine
Trileptal

Available forms
Available by prescription only
Oral suspension: 60 mg/ml
Tablets (film-coated): 150 mg, 300 mg, 600 mg

Indications and dosages
 Adjunctive therapy for partial seizures in patients with epilepsy. Adults: Initially, 300 mg P.O. b.i.d. Increase by a maximum of 600 mg daily (300 mg P.O b.i.d.) at weekly intervals. Recommended daily dose is 1,200 mg P.O. divided b.i.d.
Children ages 4 to 16: Initially 8 to 10 mg/kg daily P.O. divided b.i.d., not to exceed 600 mg daily. The target maintenance dose depends on patient weight and should be divided b.i.d. If patient weighs 20 to 29 kg (44 to 64 lb), then the target maintenance dose is 900 mg daily. If patient weighs 29.1 to 39 kg (65 to 86 lb), target maintenance dose is 1,200 mg daily. If patient weighs more than 39 kg, target maintenance dose is 1,800 mg daily. Target doses should be achieved over 2 weeks.
 Conversion to monotherapy for partial seizures in patients with epilepsy. Adults: Initially, 300 mg P.O. b.i.d., with simultaneous reduction in antiepileptic dosage. Increase oxcarbazepine by a maximum of 600 mg daily at weekly intervals over 2 to 4 weeks. Recommended daily dose is 2,400 mg P.O. divided b.i.d. Concomitant antiepileptics should be withdrawn over 3 to 6 weeks.
 Monotherapy for partial seizures in patients with epilepsy. Adults: Initially, 300 mg P.O. b.i.d. Increase dosage by 300 mg daily every third day to a daily dose of 1,200 mg divided b.i.d.
≡ Dosage adjustment. For adults with creatinine clearance less than 30 ml/minute, start with 150 mg P.O. b.i.d. (half the usual starting dose) and increase slowly to achieve the desired response.

Pharmacodynamics
Anticonvulsant action: Unknown. Antiseizure activity is thought to occur through the blockade of voltage-sensitive sodium channels which ultimately may prevent seizure spread in the brain. Increased potassium conductance and modulation of high-voltage activated calcium channels may also contribute to anticonvulsant effects.

Pharmacokinetics
Absorption: Completely absorbed.
Distribution: About 40% of 10-monohydroxy (MHD) metabolite is bound to serum proteins, mostly to albumin.
Metabolism: Oxcarbazepine is rapidly metabolized in the liver to MHD, which is mainly responsible for drug effects. About 4% of the dose is oxidized to the pharmacologically inactive 10,11-dihydroxy metabolite.
Excretion: Oxcarbazepine and its metabolites are primarily excreted by the kidneys. More than 95% appears in urine, with less than 1% as unchanged oxcarbazepine. Fecal excretion accounts for less than 4%. Half-life of parent compound is about 2 hours, and half-life of MHD is about 9 hours. Children younger than age 8 have about 30% to 40% increased clearance of drug.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components. Use cautiously in patients who have had hypersensitivity reactions to carbamazepine.

Interactions
Drug-drug. Carbamazepine, valproic acid, verapamil: Decreases levels of the active metabolite of oxcarbazepine. Monitor patient and serum levels closely.
Felodipine: Decreases felodipine level. Monitor patient closely.
Hormonal contraceptives: Decreases plasma levels of ethinylestradiol and levonorgestrel, rendering hormonal contraceptives less effective. Women of childbearing age should use alternative forms of contraception.
Phenobarbital: Decreases serum levels of the active metabolite of oxcarbazepine and increases phenobarbital level. Monitor patient closely.
Phenytoin: Decreases serum levels of the active metabolite of oxcarbazepine. May increase phenytoin level in adults receiving high doses of oxcarbazepine. Monitor phenytoin levels closely when starting therapy in these patients.
Drug-lifestyle. Alcohol use: Increased CNS depression. Avoid use together.

Adverse reactions
CNS: fatigue, asthenia, feeling abnormal, headache, dizziness, somnolence, ataxia, abnormal gait, insomnia, tremor, nervousness, agitation, abnormal coordination, speech disorder, confusion, anxiety, amnesia, aggravated seizures, hypoesthesia, emotional lability, impaired concentration, vertigo, fever.
CV: hypotension, edema, chest pain.
EENT: nystagmus, diplopia, abnormal vision, abnormal accommodation, rhinitis, sinusitis, pharyngitis, epistaxis, ear ache.
GI: nausea,vomiting,abdominal pain, diarrhea, dyspepsia, constipation, gastritis, anorexia, dry mouth, rectal hemorrhage, taste perversion, thirst.
GU: urinary tract infection, urinary frequency, vaginitis.
Metabolic: hyponatremia, weight increase.
Musculoskeletal: muscle weakness, back pain.
Respiratory: upper respiratory tract infection, cough, bronchitis, chest infection.
Skin: acne, hot flushes, purpura, rash, bruising, increased sweating.
Other: allergy, toothache, infection, lymphadenopathy.

Effects on lab test results
• May decrease sodium and thyroxine levels.

Overdose and treatment
Give symptomatic and supportive treatment as appropriate. There is no specific antidote. Consider removing drug by gastric lavage, inactivating it with activated charcoal, or both.

Special considerations
 ALERT Question patient about history of hypersensitivity to carbamazepine because 25% to 30% of these patients may develop hypersensitivity to oxcarbazepine. Stop drug immediately if signs or symptoms of hypersensitivity occur.
• Oxcarbazepine has been linked to several nervous system-related adverse events, including psychomotor slowing, difficulty with concentration, speech or language problems, somnolence, and fatigue, and coordination abnormalities, such as ataxia and gait disturbances.
• Shake suspension well before administration. Suspension can be mixed with water or may be swallowed directly from the syringe.
• Oral suspension and tablets may be interchanged at equal doses.
• Monitor serum sodium levels in patients receiving oxcarbazepine for maintenance treatment, especially those who receive other therapies that may decrease serum sodium levels.
• Monitor patient for signs and symptoms of hyponatremia, including nausea, malaise, headache, lethargy, confusion, or decreased sensation.
 ALERT Withdraw drug gradually to minimize risk of increased seizure frequency.
Breast-feeding patients
• The drug and its active metabolite appear in breast milk. Because of the risk of serious adverse reactions in infants, a decision must be made to stop either drug or breast-feeding.
Pediatric patients
• Oxcarbazepine is indicated only for adjunctive therapy in children ages 4 to 16.
Geriatric patients
• Doses may need to be adjusted in elderly patients to compensate for age-related decreases in creatinine clearance.

Patient education
• Tell patient that drug may be taken with or without food.
• Advise patient not to interrupt or stop drug without medical approval.
• Urge patient to report signs and symptoms of hyponatremia, such as nausea, malaise, headache, lethargy or confusion.
• Caution patient to avoid hazardous activities until drug effects are known.
• Advise women using hormonal contraceptives for birth control to use another form of contraception during therapy.
• Tell patient to avoid alcohol while taking drug.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use