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Medication Safety Issues
Sound-alike/look-alike issues:
OXcarbazepine may be confused with carBAMazepine
Trileptal® may be confused with TriLipix™
Pronunciation
(ox car BAZ e peen)
U.S. Brand Names
Index Terms
Generic Available
Yes: Tablet
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children ?4 years of age with epilepsy; adjunctive therapy in the treatment of partial seizures in children ?2 years of age with epilepsy
Use: Unlabeled/Investigational
Bipolar disorder; treatment of neuropathic pain
Pregnancy Risk Factor
C
Pregnancy Considerations
Oxcarbazepine crosses the human placenta. Teratogenic effects have been observed in animal studies. There are no adequate and well-controlled studies in pregnant women; however, oxcarbazepine is structurally related to carbamazepine (teratogenic in humans); use during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. Nonhormonal forms of contraception should be used during therapy.Patients exposed to oxcarbazepine during pregnancy are encouraged to enroll themselves into the AED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Oxcarbazepine and its active metabolite (MHD) are excreted in human breast milk. A milk-to-plasma concentration ratio of 0.5 was found for both. Because of the potential for serious adverse reactions to oxcarbazepine in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug in nursing women.
Contraindications
Hypersensitivity to oxcarbazepine or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• CNS effects: Use has been associated with CNS-related adverse events, most significant of these were cognitive symptoms including psychomotor slowing, difficulty with concentration, and speech or language problems, somnolence or fatigue, and coordination abnormalities, including ataxia and gait disturbances. Caution patients about performing tasks which require mental alertness (eg, operating machinery or driving).
• Dermatologic reactions: Potentially serious, sometimes fatal, dermatologic reactions (eg, Stevens-Johnson, toxic epidermal necrolysis) have been reported in adults and children; monitor for signs and symptoms of skin reactions; discontinuation and conversion to alternate therapy may be required.
• Hypersensitivity reactions: Rare cases of anaphylaxis and angioedema have been reported, even after initial dosing; permanently discontinue should symptoms occur. Use caution in patients with previous hypersensitivity to carbamazepine (cross-sensitivity occurs in 25% to 30%). Potentially serious, sometimes fatal multiorgan hypersensitivity reactions have also been reported; monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, and/or hematologic organ systems; discontinuation and conversion to alternate therapy may be required.
• Hyponatremia: Clinically-significant hyponatremia (sodium <125 mmol/L) can develop during use; monitor serum sodium, particularly during the first 3 months of therapy or in patients at risk for hyponatremia.
• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ?24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.
Disease-related concerns:
Renal impairment: Single-dose studies show that half-life of the primary active metabolite is prolonged 3-4 fold and AUC is doubled in patients with Clcr <30 mL/minute; dose adjustment required in these patients.
Concurrent drug therapy issues:
• Oral contraceptives: May reduce the efficacy of oral contraceptives; nonhormonal contraceptive measures are recommended.
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
Special populations:
• Pediatric: Safety and efficacy in children <2 years of age have not been established.
Other warnings/precautions:
• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Adverse Reactions
As reported in adults with doses of up to 2400 mg/day (includes patients on monotherapy, adjunctive therapy, and those not previously on AEDs); incidence in children was similar.
>10%:
Central nervous system: Dizziness (22% to 49%), somnolence (20% to 36%), headache (13% to 32%), ataxia (5% to 31%), fatigue (12% to 15%), vertigo (6% to 15%)
Gastrointestinal: Vomiting (7% to 36%), nausea (15% to 29%), abdominal pain (10% to 13%)
Neuromuscular & skeletal: Abnormal gait (5% to 17%), tremor (3% to 16%)
Ocular: Diplopia (14% to 40%), nystagmus (7% to 26%), abnormal vision (4% to 14%)
1% to 10%:
Cardiovascular: Hypotension (1% to 2%), leg edema (1% to 2%)
Central nervous system: Nervousness (2% to 5%), amnesia (4%), abnormal thinking (2% to 4%), insomnia (2% to 4%), speech disorder (1% to 3%), EEG abnormalities (2%), abnormal feelings (1% to 2%), agitation (1% to 2%), confusion (1% to 2%)
Dermatologic: Rash (4%), acne (1% to 2%)
Endocrine & metabolic: Hyponatremia (1% to 3%)
Gastrointestinal: Diarrhea (5% to 7%), dyspepsia (5% to 6%), constipation (2% to 6%), gastritis (1% to 2%), weight gain (1% to 2%)
Neuromuscular & skeletal: Weakness (3% to 6%), back pain (4%), falling down (4%), abnormal coordination (1% to 4%), dysmetria (1% to 3%), sprains/strains (2%), muscle weakness (1% to 2%)
Ocular: Abnormal accommodation (2%)
Respiratory: Upper respiratory tract infection (7%), rhinitis (2% to 5%), chest infection (4%), epistaxis (4%), sinusitis (4%)
Postmarketing and/or case reports (limited to important or life-threatening): Aggressive reaction, amylase increased, anaphylaxis, angioedema, aphasia, asthma, aura, biliary pain, blood in stool, bradycardia, bruising, cardiac failure, cataract, cerebral hemorrhage, chest pain, cholelithiasis, colitis, conjunctival hemorrhage, consciousness decreased, convulsions aggravated, delirium, delusion, duodenal ulcer, dysphagia, dysphonia, dyspnea, dystonia, dysuria, emotional lability, enteritis, erythema multiforme, erythematosus rash, esophagitis, eye edema, extrapyramidal disorder, facial rash, gastric ulcer, GGT increased, gingival bleeding, hematuria, hemianopia, hemiplegia, hematemesis, hot flushes, hyper-/hypoglycemia, hyper-/hypokinesia, hyper-/hyporeflexia, hypersensitivity reaction, hyper-/hypotonia, hypertension, hypocalcemia, hypochondrium pain, hypoesthesia, hypokalemia, hysteria, intermenstrual bleeding, laryngismus, leukopenia, leukorrhea, lipase increased, liver enzymes elevated, maculopapular rash, manic reaction, migraine, menorrhagia, multiorgan hypersensitivity (eosinophilia, arthralgia, rash, fever, lymphadenopathy), muscle contractions (involuntary), mydriasis, neuralgia, oculogyric crisis, otitis externa, palpitation, pancreatitis, panic disorder, paralysis, paroniria, photophobia, photosensitivity reaction, pleurisy, postural hypotension, priapism, purpura, psychosis, ptosis, rectal hemorrhage, renal calculus, renal pain, rigors, scotoma, sialoadenitis, Stevens-Johnson syndrome, stupor, suicidal behavior/ideation, syncope, systemic lupus erythematosus, tachycardia, tetany, thrombocytopenia, toxic epidermal necrolysis, ulcerative stomatitis, urinary tract pain, urticaria, vitiligo, weight loss, xerophthalmia
Metabolism/Transport Effects
Inhibits CYP2C19 (weak); Induces CYP3A4 (strong)
Drug Interactions
CYP3A4 Substrates: CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Risk X: Avoid combination
Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers, but if strong CYP3A4 inducers cannot be avoided, consider gradually (in 5 mg increments) increasing the everolimus dose from 10 mg/day to 20 mg/day (adult doses). Risk X: Avoid combination
Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Maraviroc adult dose should be increased to 600 mg twice daily when used with strong CYP3A4 inducers. This recommendation only applies in the absence of a concurrent strong CYP3A4 inhibitor (e.g., most protease inhibitors). Risk D: Consider therapy modification
Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. Risk X: Avoid combination
Oral Contraceptive (Estrogens): OXcarbazepine may decrease the serum concentration of Oral Contraceptive (Estrogens). Contraceptive failure is possible. Risk D: Consider therapy modification
Oral Contraceptive (Progestins): OXcarbazepine may decrease the serum concentration of Oral Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Pazopanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pazopanib. Risk X: Avoid combination
PHENobarbital: May decrease the serum concentration of OXcarbazepine. Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of OXcarbazepine. OXcarbazepine may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Sorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sorafenib. Risk D: Consider therapy modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed. Risk X: Avoid combination
Valproic Acid: May decrease the serum concentration of OXcarbazepine. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Herb/Nutraceutical: St John's wort may decrease oxcarbazepine levels. Avoid evening primrose (seizure threshold decreased). Avoid valerian, St John's wort, kava kava, gotu kola.
Storage
Store tablets and suspension at 25°C (77°F). Use suspension within 7 weeks of first opening container.
Mechanism of Action
Pharmacological activity results from both oxcarbazepine and its monohydroxy metabolite (MHD). Precise mechanism of anticonvulsant effect has not been defined. Oxcarbazepine and MHD block voltage-sensitive sodium channels, stabilizing hyperexcited neuronal membranes, inhibiting repetitive firing, and decreasing the propagation of synaptic impulses. These actions are believed to prevent the spread of seizures. Oxcarbazepine and MHD also increase potassium conductance and modulate the activity of high-voltage activated calcium channels.
Pharmacodynamics/Kinetics
Absorption: Complete; food has no affect on rate or extent
Distribution: MHD: Vd: 49 L
Protein binding, serum: MHD: 40%
Metabolism: Hepatic to 10-monohydroxy metabolite (MHD; active); MHD is further glucuronidated or oxidized to a 10,11-dihydroxy metabolite (DHD; inactive)
Bioavailability: Decreased in children <8 years; increased in elderly >60 years
Half-life elimination: Parent drug: 2 hours; MHD: 9 hours; renal impairment (Clcr 30 mL/minute): MHD: 19 hours
Clearance of MHD is increased in younger children (~80% in children 2-4 years of age) and approaches that of adults by ~13 years of age
Time to peak, serum (median): Tablets: 4.5 hours; oral suspension: 6 hours
Excretion: Urine (95%, <1% as unchanged oxcarbazepine, 27% as unchanged MHD, 49% as MHD glucuronides); feces (<4%)
Dosage
Oral:
Children 2-3 years:
Adjunctive therapy: 8-10 mg/kg/day, not to exceed 600 mg/day, given in 2 divided daily doses. Maintenance dose should be achieved over 2 weeks, and is dependent upon patient weight.
<20 kg: Consider initiating dose at 16-20 mg/kg/day; maximum maintenance dose should be achieved over 2-4 weeks and should not exceed 60 mg/kg/day
Children 4-16 years:
Adjunctive therapy: 8-10 mg/kg/day, not to exceed 600 mg/day, given in 2 divided daily doses. Maintenance dose should be achieved over 2 weeks, and is dependent upon patient weight, according to the following:
20-29 kg: 900 mg/day in 2 divided doses
29.1-39 kg: 1200 mg/day in 2 divided doses
>39 kg: 1800 mg/day in 2 divided doses
Children 4-16 years:
Conversion to monotherapy: Oxcarbazepine 8-10 mg/kg/day in twice daily divided doses, while simultaneously initiating the reduction of the dose of the concomitant antiepileptic drug; the concomitant drug should be withdrawn over 3-6 weeks. Oxcarbazepine dose may be increased by a maximum of 10 mg/kg/day at weekly intervals. See below for recommended total daily dose by weight.
Initiation of monotherapy: Oxcarbazepine should be initiated at 8-10 mg/kg/day in twice daily divided doses; doses may be titrated by 5 mg/kg/day every third day. See below for recommended total daily dose by weight.
Range of maintenance doses by weight during monotherapy:
20 kg: 600-900 mg/day
25-30 kg: 900-1200 mg/day
35-40 kg: 900-1500 mg/day
45 kg: 1200-1500 mg/day
50-55 kg: 1200-1800 mg/day
60-65 kg: 1200-2100 mg/day
70 kg: 1500-2100 mg/day
Adults:
Adjunctive therapy: Initial: 300 mg twice daily; dose may be increased by as much as 600 mg/day at weekly intervals; recommended daily dose: 1200 mg/day in 2 divided doses. Although daily doses >1200 mg/day were somewhat more efficacious, most patients were unable to tolerate 2400 mg/day (due to CNS effects).
Conversion to monotherapy: Oxcarbazepine 600 mg/day in twice daily divided doses while simultaneously initiating the reduction of the dose of the concomitant antiepileptic drug. The concomitant dosage should be withdrawn over 3-6 weeks, while the maximum dose of oxcarbazepine should be reached in about 2-4 weeks. Recommended daily dose: 2400 mg/day.
Initiation of monotherapy: Oxcarbazepine should be initiated at a dose of 600 mg/day in twice daily divided doses; doses may be titrated upward by 300 mg/day every third day to a final dose of 1200 mg/day given in 2 daily divided doses
Dosing adjustment in renal impairment: Clcr <30 mL/minute: Therapy should be initiated at one-half the usual starting dose (300 mg/day in adults) and increased slowly to achieve the desired clinical response
Dosing adjustment in hepatic impairment: Adjustment not needed for mild-to-moderate impairment. No data in patients with severe impairment.
Administration: Oral
Suspension: Prior to using for the first time, firmly insert the plastic adapter provided with the bottle. Cover adapter with child-resistant cap when not in use. Shake bottle for at least 10 seconds, remove child-resistant cap, and insert the oral dosing syringe provided to withdraw appropriate dose. Dose may be taken directly from oral syringe or may be mixed in a small glass of water immediately prior to swallowing. Rinse syringe with warm water after use and allow to dry thoroughly. Discard any unused portion after 7 weeks of first opening bottle.
Monitoring Parameters
Seizure frequency, serum sodium (particularly during first 3 months of therapy), symptoms of CNS depression (dizziness, headache, somnolence). Additional serum sodium monitoring recommended during maintenance treatment in patients receiving other medications known to decrease sodium levels, in patients with signs/symptoms of hyponatremia, and in patients with an increase in seizure frequency or severity. Monitor for suicidality (eg, suicidal thoughts, depression, behavioral changes).
Test Interactions
Thyroid function tests may depress serum T4 without affecting T3 levels or TSH.
Dietary Considerations
May be taken without regard to meals.
Patient Education
Do not increase dose or frequency or discontinue without consulting prescriber. While using the medication, do not use alcohol and other prescription or OTC medications (especially medications to relieve pain, induce sleep, reduce anxiety, treat or prevent cold, coughs, or allergies) unless approved by prescriber. Maintain adequate hydration unless instructed to restrict fluid intake. You may experience drowsiness, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea or vomiting (small frequent meals, good mouth care, chewing gum, or sucking hard candy may help, or contact prescriber). Report CNS changes, increase in seizure frequency or severity, mentation changes, suicidal ideation, depression, changes in cognition or memory, persistent fever, acute fatigue or weakness, or insomnia; muscle cramping, weakness, or abdominal pain; rash or skin irritations; unusual bruising or bleeding (mouth, urine, stool); swelling of extremities; or other adverse response. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Note: Oxcarbazepine may reduce the effectiveness of oral contraceptives; nonhormonal contraception is recommended. Breast-feeding is not recommended.
Geriatric Considerations
Studies in elderly volunteers (60-82 years of age) with both single dose (300 mg) and multiple doses (600 mg/day) reported maximum plasma concentrations and AUC as being 30% to 60% higher than younger volunteers (18-32 years of age). These results were due to differences in creatinine clearance between the two groups. Since elderly may have Clcr <30 mL/minute, dose reductions may be needed.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Comment
Oxcarbazepine has been associated with psychomotor slowing, difficulty with concentration, speech or language problems, sedation, ataxia, and gait disturbances. Because this agent is the 10-keto analog of carbamazepine, it is often considered useful for the management of bipolar disorder. However, there is a paucity of research data supporting this usage.
Nursing: Physical Assessment/Monitoring
Assess complete allergy history (carbamazepine). Assess effectiveness and interactions of other medications. Monitor therapeutic effectiveness (seizure activity, frequency, duration, type), laboratory results, and adverse reactions (eg, sedation, CNS changes, visual changes). Monitor for skin reactions. Dosage should be tapered when discontinuing to reduce risk of increased seizures. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse reactions to report. Note: Oxcarbazepine may reduce the effectiveness of oral contraceptives; nonhormonal contraception is recommended.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, oral:
Trileptal®: 300 mg/5 mL (250 mL) [contains ethanol; packaged with oral syringe]
Tablet: 150 mg, 300 mg, 600 mg
Trileptal®: 150 mg, 300 mg, 600 mg
Pricing: U.S. (www.drugstore.com)
Suspension (Trileptal)
300 mg/5 mL (250): $170.60
Tablets (OXcarbazepine)
150 mg (30): $45.99
300 mg (60): $129.99
600 mg (60): $259.98
Tablets (Trileptal)
150 mg (60): $108.52
300 mg (60): $197.78
600 mg (60): $362.62
References
American Academy of Pediatrics Committee on Drugs, “The Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
Carrazana E and Mikoshiba I, “Rationale and Evidence for the Use of Oxcarbazepine in Neuropathic Pain,” J Pain Symptom Manage, 2003, 25(5 Suppl):31-5.
Irving GA, “Contemporary Assessment and Management of Neuropathic Pain,” Neurology, 2005, 28;64(12 Suppl 3):21-7.
Myllynen P, Pienimaki P, Jouppila P, et al, “Transplacental Passage of Oxcarbazepine and its Metabolites in vivo,” Epilepsia, 2001, 42(11):1482-5.
Rey E, Bulteau C, Motte J, et al, “Oxcarbazepine Pharmacokinetics and Tolerability in Children With Inadequately Controlled Epilepsy,” J Clin Pharmacol, 2004, 44(11):1290-300.
Suppes T, Dennehy EB, Hirschfeld RMA, et al, “The Texas Implementation of Medication Algorithms: Update to the Algorithms for the Treatment of Bipolar I Disorder,” J Clin Psychiatry, 2005, 66(7):870-86.
International Brand Names
Lexi-Comp.com
Last full review/revision November 2009
Content last modified November 2009
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