oxcarbazepine

Absorption: Rapidly absorbed after oral administration and rapidly converted to the active 10-hydroxy metabolite (MHD).

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Extensively converted to the active metabolite, MHD, which is then primarily excreted by the kidneys.

Half-Life: Oxcarbazepine: 2 hr; MHD: 9 hr.

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	PO	rapid	4.5 hr‡

‡Steady-state levels of MHD are reached after 2–3 days during twice-daily dosing.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to oxcarbazepine, carbamazepine, or eslicarbazepine.

Use Cautiously in:

All patients (may ↑ risk of suicidal thoughts/behaviors);
Renal impairment (dose ↓ recommended if CCr <30 mL/min);
Severe hepatic impairment;
Rep: Women of reproductive potential;
OB: May be teratogenic (associated with oral clefts and cardiac abnormalities); levels of active metabolites may gradually during pregnancy which may seizure risk; use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children 2 yr (immediate-release) or 6 yr (extended-release);
Geri: Appears on Beers list. May worsen or cause syndrome of inappropriate antidiuretic hormone (SIADH) secretion in older adults. Use with caution in older adults and closely monitor sodium concentrations when starting therapy or dose.

Patients positive for HLA-B*1502 alleles (unless benefits clearly outweigh the risks) (↑ risk of serious skin reactions).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: acne, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria

EENT: abnormal vision, diplopia, nystagmus

Endo: SIADH, hypothyroidism

F and E: ↑thirst, hyponatremia

GI: abdominal pain, nausea, vomiting, dyspepsia

Hemat: lymphadenopathy

Neuro: ataxia, dizziness, drowsiness, gait disturbances, headache, tremor, vertigo, cognitive symptoms, SEIZURES, SUICIDAL THOUGHTS

Misc: hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

May ↑ levels and risk of toxicity of CYP2C19 substrates, including phenytoin when used at doses greater than 1200 mg/day; may need to ↓ dose of phenytoin.
May ↓ levels and effectiveness of CYP3A4 substrates, including hormonal contraceptives.
Carbamazepine, phenobarbital, phenytoin, and rifampin may ↓ levels; monitor MHD levels during titration period; may need to adjust dose of oxcarbazepine.

Route/Dosage ⬆ ⬇

(Immediate-release tablets and oral suspension can be interchanged at equal doses.)
PO (Adults ): Adjunctive therapy (immediate-release): 300 mg twice daily, may ↑ by up to 600 mg/day at weekly intervals up to 1200 mg/day (up to 2400 mg/day may be needed); Conversion to monotherapy (immediate-release): 300 mg twice daily; may ↑ by 600 mg/day at weekly intervals, while other antiepileptic drugs are tapered over 3–6 wk; dose of oxcarbazepine should be ↑ up to 2400 mg/day over a period of 2–4 wk; Initiation of monotherapy (immediate-release): 300 mg twice daily, ↑ by 300 mg/day every 3rd day, up to 1200 mg/day. Maximum maintenance dose should be achieved over 2–4 wk; Adjunctive therapy or monotherapy (extended-release): 600 mg once daily for 1 wk; may ↑ by 600 mg/day at weekly intervals up to 1200–2400 mg once daily; Concurrent use of strong CYP3A4 inducer (carbamazepine, phenobarbital, phenytoin, rifampin) (extended-release): consider initiating therapy with 900 mg once daily.
PO (Children 2–16 yr): Adjunctive therapy (immediate-release): 4–5 mg/kg twice daily (up to 600 mg/day), ↑ over 2 wk to achieve 900 mg/day in patients 20–29 kg, 1200 mg/day in patients 29.1–39 kg and 1800 mg/day in patients >39 kg (range 6–51 mg/kg/day). In patients <20 kg, initial dose of 16–20 mg/kg/day may be used not to exceed 60 mg/kg/day. Conversion to monotherapy (immediate-release): 8–10 mg/kg/day given twice daily; may ↑ by 10 mg/kg/day at weekly intervals, whereas other antiepileptic drugs are tapered over 3–6 wk; dose of oxcarbazepine should be ↑ up to 600–900 mg/day in patients ≤20 kg, 900–1200 mg/day in patients 25–30 kg, 900–1500 mg/day in patients 35–40 kg. 1200–1500 mg/day in patients 45 kg, 1200–1800 mg/day in patients 50–55 kg, 1200–2100 mg/day in patients 60–65 kg, and 1500–2100 mg/day in patients 70 kg. Maximum maintenance dose should be achieved over 2–4 wk.
PO (Children 6–17 yr): Adjunctive therapy or monotherapy (extended-release): 8–10 mg/kg once daily (up to 600 mg/day) for 1 wk; may ↑ by 8–10 mg/kg/day at weekly intervals over 2–3 wk to achieve 900 mg/day in patients 20–29 kg, 1200 mg/day in patients 29.1–39 kg and 1800 mg/day in patients >39 kg; Concurrent use of strong CYP3A4 inducer (carbamazepine, phenobarbital, phenytoin, rifampin) (extended-release): consider initiating therapy with 12–15 mg/kg (max dose = 900 mg) once daily.

Renal Impairment

PO (Adults ): CCr<30 mL/min (immediate- and extended-release). Initiate therapy at 300 mg/day and ↑ slowly to achieve desired response.

Availability ⬆ ⬇

(Generic available)

Immediate-release tablets: 150 mg; 300 mg; 600 mg
Extended-release tablets: 150 mg; 300 mg; 600 mg
Oral suspensionlemon-flavor: 300 mg/5 mL

Assessment ⬆ ⬇

Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
Seizures: Assess frequency, location, duration, and characteristics of seizure activity. Hyponatremia may increase frequency and severity of seizures.
Monitor patient for CNS changes. May manifest as cognitive symptoms (psychomotor slowing, difficulty with concentration, speech or language problems), somnolence or fatigue, or coordination abnormalities (ataxia, gait disturbances).
Monitor for skin reactions (rash, erythema, urticaria, pruritus, fever, blistering). Patients with HLA-B*1502 alleles are at increased risk for Stevens-Johnson syndrome and toxic epidermal necrolysis. Discontinue oxcarbazepine if symptoms occur.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling), associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

Lab Test Considerations:

Monitor ECG and serum electrolytes before and periodically during therapy. May cause hyponatremia. Usually occurs during the first 3 mo of therapy. May require dose reduction, fluid restriction, or discontinuation of therapy. Sodium levels return to normal within a few days of discontinuation.

Implementation ⬆ ⬇

Do not confuse oxcarbazepine with carbamazepine or oxaprozin.
Implement seizure precautions as indicated.
PO: Administer twice daily with or without food.
- Administer extended-release tablets on an empty stomach, at least 1 hr before or 2 hr after meals; giving with food increases risks of adverse effects. DNC: Swallow extended-release tablets whole, do not crush, break, or chew.
- Shake oral suspension well and prepare dose immediately after. Withdraw using oral dosing syringe supplied by manufacturer. May be mixed in a small glass of water just prior to administration or swallowed directly from syringe. Rinse syringe with warm water and allow to dry.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take oxcarbazepine in equally spaced doses, as directed. Take missed doses as soon as possible but not just before next dose; do not double dose. Notify health care professional if more than 1 dose is missed. Medication should be gradually discontinued to prevent seizures. Instruct patient to read the Medication Guide before starting and with each Rx refill, changes may occur.
- May cause dizziness, drowsiness, or CNS changes. Advise patients to avoid driving or other activities requiring alertness until response to medication is known. Do not resume driving until physician gives clearance based on control of seizure disorder.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications. Advise patient not to take alcohol or other CNS depressants, including opioids, concurrently with this medication.
- Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking, other unusual changes in behavior or mood occur.
- Instruct patient to notify health care professional of medication regimen before treatment or surgery.
Rep: Advise females of reproductive potential to use an additional nonhormonal method of contraception during therapy and until next menstrual period. Instruct patient to notify health care professional if pregnancy is planned or suspected. Encourage patients who become pregnant to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334 or on the web at www.aedpregnancyregistry.org. Enrollment must be done by patients themselves.
Advise patients to carry identification describing disease and medication regimen at all times.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇