Trade Names:Trileptal- Tablets 150 mg- Tablets 300 mg- Tablets 600 mg- Suspension, oral 60 mg/mLApo-Oxcarbazepine (Canada)
The pharmacologic activity is primarily through the 10-monohydroxy metabolite (MHD) of oxcarbazepine, but the exact mechanism is unknown. It may block voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminution of propagation of synaptic impulses.
Completely absorbed and extensively metabolized to active MHD. In steady state, MHD is reached in 2 to 3 days when given twice daily. For tablet form, T max is 4.5 h. For oral suspension form, T max is 6 h.
The Vd for MHD is 49 L. 40% of serum is protein bound for the MHD, predominantly albumin.
Rapidly reduced by cytosolic enzymes in the liver to MHD, which is primarily responsible for pharmacologic effect. MHD metabolized further by conjugation with glucuronic acid. 4% oxidized to inactive 10,11-dihydroxy metabolite (DHD).
Less than 1% eliminated unchanged through the kidneys. 80% excreted as glucuronides of MHD (49%) or as unchanged MHD (27%); inactive DHD accounts for 3%, and conjugates of MHD and oxcarbazepine account for 13%. The t ½ for the parent drug is approximately 2 h. The t ½ for MHD is approximately 9 h.
If less CrCl than 30 mL/min, elimination t ½ of MHD is prolonged to 19 h; 2-fold increase in AUC. Dose adjustment recommended.Elderly
Max plasma concentration and AUC values of MHD were 30% to 60% higher.
As monotherapy or adjunctive therapy in the treatment of partial seizures in adults; as monotherapy in the treatment of partial seizures in children 4 yr of age and older with epilepsy; as adjunctive therapy in children 2 yr of age and older with epilepsy.
Alternative treatment for bipolar disorder, diabetic neuropathy.
PO Initial dose of 300 mg twice daily; may be increased by a max of 600 mg/day at weekly intervals. Recommended daily dose is 1,200 mg/day.Children 4 to 16 yr of age
PO Initial dose of 8 to 10 mg/kg, generally not to exceed 600 mg/day, given twice daily; target maintenance dose should be achieved over 2 wk and is dependent upon patient weight (900 mg/day for 20 to 29 kg; 1,200 mg/day for 29.1 to 39 kg; 1,800 mg/day for more than 39 kg).Children 2 to younger than 4 yr of age
PO Initial dose of 8 to 10 mg/kg/day not to exceed 600 mg/day given in 2 divided doses. For children less than 20 kg, consider a starting dose of 16 to 20 mg/kg. The max maintenance dose should be achieved in 2 to 4 wk and should not exceed 60 mg/kg/day given in a twice-a-day regimen.Conversion to MonotherapyAdults
PO Initial dose of 300 mg twice daily while simultaneously initiating dose reduction of the concomitant antiepileptic drugs (AEDs). These should be completely withdrawn over 3 to 6 wk while the max dose of the oxcarbazepine should be reached in 2 to 4 wk. Oxcarbazepine may be increased 600 mg/day at weekly intervals; recommended daily dose is 2,400 mg/day.Children 4 to 16 yr of age
PO Initial dose of 8 to 10 mg/kg/day given in 2 divided doses while simultaneously reducing the dose of concomitant AEDs. The AEDs can be completely withdrawn over 3 to 6 wk while oxcarbazepine may be increased by a max increment of 10 mg/kg/day at weekly intervals.Initiation of MonotherapyAdults
PO Initial dose of 300 mg twice daily; increase dose every 3 days by 300 mg/day to a dose of 1,200 mg/day.Children 4 to 16 yr of age
PO Initial dose of 8 to 10 mg/kg/day given in 2 divided doses. The dose may be increased by 5 mg/kg/day every 3 days to the maintenance dose based on the following body weights:
(CrCl less than 30 mL/min): Initiate therapy at 50% of the starting dose; titrate more slowly until the desired response is achieved.
Store tablets and suspension at controlled room temperature (59° to 86°F). Discard any unused suspension 7 wk after first opening.
May inhibit CYP2C19 and induce CYP3A4/5.Carbamazepine
May decrease MHD.Contraceptives, oral
May decrease ethinyl estradiol and levonorgestrel AUC.Felodipine
May decrease felodipine AUC.Lamotrigine
Levels may be reduced by oxcarbazepine.Phenobarbital
May decrease MHD and may increase phenobarbital AUC.Phenytoin
May decrease MHD and may increase phenytoin AUC.Valproic acid
May decrease MHD AUC.Verapamil
May decrease MHD.
None well documented.
The incidences stated for the following adverse reactions were reported with oxcarbazepine monotherapy.
Dizziness (49%); somnolence (36%); headache (32%); ataxia (31%); fatigue (21%); gait abnormal (17%); tremor (16%); vertigo (15%); emotional lability (8%); anxiety, confusion, nervousness (7%); insomnia (6%); aggravated convulsion, amnesia (5%); abnormal coordination, abnormal thinking (4%); hyperesthesia, speech disorder (3%); agitation, convulsions, cranial injury not otherwise specified, dysmetria, EEG abnormal, impaired concentration, involuntary muscle contractions (2%).
Chest pain, hypotension (2%).
Rash (4%); acne, hot flushes, purpura (2%).
Diplopia (40%); nystagmus (26%); abnormal vision (14%); taste perversion (5%); ear infection, earache (2%).
Vomiting (36%); nausea (29%); abdominal pain (13%); diarrhea (7%); constipation, dyspepsia (6%); anorexia (5%); dry mouth (3%); gastritis, rectum hemorrhage, toothache (2%).
UTI (5%); micturition frequency, vaginitis (2%).
Hyponatremia (5%); lymphadenopathy (2%).
Back pain (4%); muscle weakness, sprains and strains (2%)
Rhinitis, upper respiratory tract infection (10%); coughing (5%); chest infection, epistaxis, sinusitis (4%); bronchitis, pharyngitis (3%); pneumonia (2%).
Viral infection (7%); asthenia (6%); bruising, falling down (4%); fever, increased sweating, vertigo (3%); accommodation abnormal, allergy, asthenia, edema (legs), feeling abnormal, generalized edema, infection, weight increase (2%); erythema multiforme, multiorgan hypersensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (postmarketing).
Serum sodium levels during maintenance treatment.
Category C .
Oxcarbazepine and MHD are excreted in breast milk. Effects on infant are undetermined.
Safety and efficacy not established in children younger than 2 yr of age (adjunctive therapy). Safety and efficacy not established in children younger than 4 yr of age (monotherapy).
Because of age-related reductions in CrCl, C max and AUC may be elevated.
Approximately 25% to 30% of patients who have a hypersensitivity to carbamazepine will experience a hypersensitivity reaction to oxcarbazepine.
Use with caution; dosage adjustment may be required (see Dosage).
Oxcarbazepine has been associated with psychomotor slowing; difficulty with concentration, speech, or language; somnolence or fatigue; and coordination abnormalities, including ataxia and gait disturbances.
Withdraw therapy gradually to minimize potential of increased seizure frequency.
Oxcarbazepine has been associated with Stevens-Johnson syndrome and toxic epidermal necrolysis. If a patient develops a skin reaction, discontinue use.
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