Oxcarbazepine (Trileptal) is an analog of carbamazepine that has better tolerability when taken orally and fewer drug-drug interactions. It is used in the management of patients with seizures.

Oxcarbazepine Uses:

Focal (partial) onset seizures:

• Immediate-release:
  • Used as monotherapy or adjunctive therapy in the treatment of focal (partial) onset seizures in adults, as monotherapy in the treatment of focal (partial) onset seizures in children ≥4 years of age with epilepsy, and as adjunctive therapy in children ≥2 years of age with focal (partial) onset seizures.
• Extended-release:
  • Treatment of focal (partial) onset seizures in adults and in children ≥6 years of age.

Off Label Use Oxcarbazepine in Adults:

• Neuropathic pain.

Oxcarbazepine Dose in Adults

Oxcarbazepine Dose in the treatment of Adjunctive therapy, focal (partial) onset seizures (epilepsy): Oral:

Immediate release:

• Initial:600 mg daily in 2 divided doses.
• The dose may be increased by as much as 600 mg per day increments at weekly intervals.
• Maximum recommended dose: 1,200 mg per day in 2 divided doses.
• Although doses >1,200 mg per day were somewhat more efficacious, most patients were unable to tolerate 2,400 mg per day (due to CNS effects).

Extended-release:

• Initial:600 mg once a day.
• Dosage may be increased by 600 mg/day increments at weekly intervals.
• The recommended daily dose is 1,200 to 2,400 mg once a day.
• Although daily doses >1,200 mg daily were somewhat more efficacious, most patients were unable to tolerate 2,400 mg daily (due to CNS effects).

Conversion to monotherapy, focal (partial) onset seizures (epilepsy): Patients receiving concomitant antiepileptic drugs (AEDs):

Oral: Immediate release:

• Initial: 600 mg daily in 2 divided doses while simultaneously reducing the dose of concomitant AEDs.
• Withdraw concomitant AEDs completely over 3 to 6 weeks, while increasing the oxcarbazepine dose in increments of 600 mg daily at weekly intervals, reaching the maximum oxcarbazepine dose (2,400 mg/day) in about 2 to 4 weeks (lower doses have been effective in patients in whom monotherapy has been initiated).

Oxcarbazepine Dose in the treatment of Initiation of monotherapy, focal (partial) onset seizures (epilepsy): Oral:

Immediate-release:

• Initial: 600 mg daily in 2 divided doses.
• Increase dose by 300 mg daily every third day to a dose of 1,200 mg daily.
• Higher dosages (2,400 mg daily) have been shown to be effective in patients converted to monotherapy from other AEDs.

Extended-release:

• Initial: 600 mg once a day.
• Dosage may be increased by 600 mg per day increments at weekly intervals.
• The recommended daily dose is 1,200 to 2,400 mg once a day.
• Although daily doses >1,200 mg per day may be somewhat more efficacious, higher doses are associated with increased adverse effects.

Conversion from immediate-release to extended-release:

• Higher doses of the extended-release formulation may be necessary.

Dosage adjustment with concomitant strong CYP3A4 inducers or UGT inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin): Extended-release:

• Consider initiating dose at 900 mg once a day.

Oxcarbazepine Dose in the treatment of Neuropathic pain (off-label):

Oral:

• Initial: 300 mg/day.
• Increase dose after 3 days to 300 mg twice a day, then adjust dose based on response and tolerability in increments of 300 mg every 5 days up to a maximum dose of 900 mg twice a day.
• The mean dose during the clinical trial maintenance period was 1,445 mg per day.

Oxcarbazepine Dose in Childrens

Note:

• Immediate-release preparations (oral suspension and tablets) are interchangeable on an mg per mg basis.
• Immediate-release and extended-release preparations are not bioequivalent and not interchangeable on an mg per mg basis.

Oxcarbazepine Dose in the treatment of Partial-onset seizures, monotherapy: Oral:

Immediate-release (Trileptal):

Children ≥4 years and Adolescents ≤16 years:

• Initiation of monotherapy: Patients not receiving concomitant anti-epileptic drugs (AEDs):

Initial: 8 to 10 mg/kg/day in 2 divided doses; usual initial daily dose in adults is 600 mg/day; increase the dose every third day by 5 mg/kg/day to achieve the recommended monotherapy maintenance dose by weight, as follows:

Maintenance dose:

• 20 to <25 kg: 600 to 900 mg/day in 2 divided doses.
• 25 to <35 kg: 900 to 1,200 mg/day in 2 divided doses.
• 35 to <45 kg: 900 to 1,500 mg/day in 2 divided doses.
• 45 to <50 kg: 1,200 to 1,500 mg/day in 2 divided doses.
• 50 to <60 kg: 1,200 to 1,800 mg/day in 2 divided doses.
• 60 to <70 kg: 1,200 to 2,100 mg/day in 2 divided doses.
• ≥70 kg: 1,500 to 2,100 mg/day in 2 divided doses.

Conversion to monotherapy:

• Patients receiving concomitant AEDs: Initial: 8 to 10 mg/kg/day in 2 divided doses (usual initial daily dose in adults is 600 mg/day), with a simultaneous initial reduction of the dose of concomitant AEDs.
• Withdraw concomitant AEDs completely over 3 to 6 weeks, while increasing oxcarbazepine dose as needed by no more than 10 mg/kg/day at approximately weekly intervals.
• Increase oxcarbazepine dose to achieve the recommended monotherapy maintenance dose.

Adolescents ≥17 years: Initiation of monotherapy: Patients not receiving prior AEDs:

• Initial: 300 mg twice a day.
• Increase dose by 300 mg per day every third day to a maintenance dose of 1,200 mg per day in 2 divided doses.

Conversion to monotherapy: Patients receiving concomitant AEDs:

• Initial: 300 mg twice daily while simultaneously reducing the dose of concomitant AEDs.
• Withdraw concomitant AEDs completely over 3 to 6 weeks, while increasing the oxcarbazepine dose in increments of 600 mg per day at weekly intervals up to target maintenance dose of 2,400 mg per day in 2 divided doses in about 2 to 4 weeks.

Oxcarbazepine Dose in the treatment of Partial-onset seizures, adjunctive therapy: Oral:

Immediate-release (Trileptal):

Children 2 to <4 years:

Patient weight <20 kg: Initial:

• 8 to 10 mg per kg per day in 2 divided doses.
• May consider initiating at a higher dose of 16 to 20 mg per kg per day due to increased clearance at this age.
• Increase dose slowly over 2 to 4 weeks.
• Maximum daily dose: 60 mg per kg per day.

Patient weight ≥20 kg:

• Initial: 8 to 10 mg per kg per day in 2 divided doses (usual maximum initial daily dose: 600 mg per day).
• Increase dose slowly over 2 to 4 weeks.
• Maximum daily dose: 60 mg per kg per day.

Note:

• In children 2 to 4 years of age, 50% of patients were titrated to a final dose of at least 55 mg per kg per day with a target dose of 60 mg per kg per day.
• Due to a higher drug clearance, children 2 to <4 years of age may require up to twice the dose per body weight compared to adults.

Children ≥4 years and Adolescents ≤16 years:

• Initial: 8 to 10 mg per kg per day in 2 divided doses.
• Usual maximum initial daily dose: 600 mg per day.
• Increase the dose slowly over 2 weeks to the target maintenance dose by weight, as follows:

Maintenance dose:

• 20 to 29 kg: 900 mg/day in 2 divided doses.
• 1 to 39 kg: 1,200 mg/day in 2 divided doses.
• >39 kg: 1,800 mg/day in 2 divided doses.

Note:

• Use of these pediatric target maintenance doses in one clinical trial resulted in doses ranging from 6 to 51 mg per kg per day (median dose: 31 mg per kg per day) in pediatric patients 4 to 16 years of age.
• Due to a higher drug clearance, children 4 to ≤12 years of age may require a 50% higher dose per body weight compared to adults.

Adolescents ≥17 years:

• Initial: 300 mg twice a day.
• The dose may be increased by ≤600 mg per day increments at weekly intervals up to a target maintenance dose of 1,200 mg per day in 2 divided doses.
• Although doses >1,200 mg per day were somewhat more efficacious, most patients were unable to tolerate 2,400 mg per day (due to CNS effects).

Extended-release (Oxtellar XR):

Children and Adolescents 6 to ≤16 years:

• Initial: 8 to 10 mg per kg per day once a day.
• Maximum initial daily dose: 600 mg per day during the first week of therapy.
• Increase dose at weekly intervals in 8 to 10 mg per kg per day increments over 2 to 3 weeks (maximum dosage incremental increase: 600 mg per dose) to the target maintenance dose based on weight, as follows:

Maintenance dose:

• 20 to 29 kg: 900 mg once a day.
• 1 to 39 kg: 1,200 mg once a day.
• >39 kg: 1,800 mg once a day.

Adolescents ≥17 years:

• Initial: 600 mg once a day.
• Dosage may be increased by 600 mg per day increments at weekly intervals.
• The recommended daily dose is 1,200 to 2,400 mg once a day.
• Although daily doses >1,200 mg daily were somewhat more efficacious, most patients were unable to tolerate 2,400 mg per day (due to CNS effects).

Conversion from immediate-release (Trileptal) to extended-release (Oxtellar XR):

• Children ≥6 years and Adolescents:
  • Higher doses of Oxtellar XR may be necessary; on an mg per mg basis dosage forms are not bioequivalent.

Dosage adjustment with concomitant drugs:

• Strong inducers of CYP3A4 and/or UGT (eg, rifampin, carbamazepine, phenytoin, phenobarbital):
• Immediate-release:
  • Children ≥2 years and Adolescents:
    • During oxcarbazepine titration, monitor serum concentrations of 10-monohydroxy (MHD) metabolite (active).
    • Additional oxcarbazepine dose adjustments may be necessary if inducer initiated, dose modified, or discontinued.

• Extended-release:
  • Children ≥6 years and Adolescents:
    • Initial: Consider higher initial doses of oxcarbazepine:
    • 6 to ≤16 years:
      • Oral: 12 to 15 mg per kg per day once a day (maximum daily dose: 900 mg per day).
    • ≥17 years:
      • Oral: 900 mg per day.
      • Additional oxcarbazepine dose adjustments may be necessary if inducer initiated, dose modified, or discontinued.

Oxcarbazepine Pregnancy Category: C

• Oxcarbazepine is the active metabolite MHD and inactive metabolite DHD. They cross the placenta and are detectable in newborns.
• According to the manufacturer data from a small number of pregnancies from pregnancy registries suggests congenital malformations related to oxcarbazepine monotherapy.
• This includes craniofacial defects as well as cardiac malformations.
• AED monotherapy is more likely to produce teratogenic effects than AED polytherapy.
• Due to the physiologic changes during pregnancy, plasma concentrations of MHD slowly decrease; patients should be closely monitored during and after delivery.
• Oxcarbazepine could lower plasma levels of hormonal contraceptives.
• Continuous data collection is underway to monitor the outcomes of oxcarbazepine-exposed infants and pregnant women.
• Patients who were exposed to oxcarbazepine in pregnancy should call 1-888-233-3233 to register for the NAAED Pregnancy Registry.
• Additional information can be found at aedpregnancyregistry.org.

Use of oxycarbazepine while breastfeeding

• Breast milk contains oxycarbazepine as well as the active 10-hydroxy metabolite MHD.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.

Oxcarbazepine Dose in Kidney Disease:

Mild-to-moderate impairment:

• In the manufacturer's labeling, there are no dosage adjustments provided.

Severe impairment (CrCl <30 mL/minute):

• Immediate release, Extended-release: Therapy should be initiated at one-half the usual starting dose (300 mg daily) and increased slowly to achieve the desired clinical response (eg, 300 to 450 mg daily at weekly intervals).

ESRD (on dialysis):

• Immediate-release formulations should be used instead of the extended-release formulation.

Oxcarbazepine dose in Liver Disease:

Mild-to-moderate impairment:

• No dosage adjustments are necessary.

Severe impairment:

• Immediate release:
  • There are no dosage adjustments provided in the manufacturer's labeling; use cautiously (has not been studied).
• Extended-release:
  • There are no dosage adjustments provided in the manufacturer's labeling; use is not recommended (has not been studied).

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• The incidence of adverse effects is from monotherapy and adjunctive AED studies.
• The incidence in children was similar.

Common Side Effects of Oxcarbazepine:

• Central Nervous System:

  • Dizziness
  • Drowsiness
  • Headache
  • Ataxia
  • Fatigue
  • Abnormal Gait
  • Vertigo

• Gastrointestinal:

  • Vomiting
  • Nausea
  • Abdominal Pain

• Neuromuscular & Skeletal:

  • Tremor

• Ophthalmic:

  • Diplopia
  • Nystagmus
  • Visual Disturbance

Less Common Side Effects Of Oxcarbazepine:

• Cardiovascular:

  • Chest Pain
  • Edema
  • Lower Extremity Edema
  • Hypotension

• Central Nervous System:

  • Emotional Lability
  • Anxiety
  • Equilibrium Disturbance
  • Confusion
  • Nervousness
  • Amnesia
  • Seizure
  • Falling
  • Abnormality In Thinking
  • Insomnia
  • Hypoesthesia
  • Dysmetria
  • Speech Disorder
  • Abnormal Electroencephalogram
  • Agitation
  • Lack Of Concentration
  • Feeling Abnormal
  • Myasthenia

• Dermatologic:

  • Skin Rash
  • Diaphoresis
  • Acne Vulgaris

• Endocrine & Metabolic:

  • Hyponatremia
  • Hot Flash
  • Increased Thirst
  • Weight Gain

• Gastrointestinal:

  • Diarrhea
  • Constipation
  • Dyspepsia
  • Anorexia
  • Dysgeusia
  • Upper Abdominal Pain
  • Xerostomia
  • Gastritis
  • Toothache

• Genitourinary:

  • Urinary Tract Infection
  • Urinary Frequency
  • Vaginitis

• Hematologic & Oncologic:

  • Bruise
  • Lymphadenopathy
  • Purpuric Rash
  • Rectal Hemorrhage

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Viral Infection
  • Infection

• Neuromuscular & Skeletal:

  • Asthenia
  • Back Pain
  • Muscle Spasm
  • Sprain

• Ophthalmic:

  • Blurred Vision
  • Accommodation Disturbance

• Otic:

  • Otalgia
  • Otic Infection

• Respiratory:

  • Upper Respiratory Tract Infection
  • Rhinitis
  • Cough
  • Epistaxis
  • Pulmonary Infection
  • Sinusitis
  • Bronchitis
  • Nasopharyngitis
  • Pharyngitis
  • Pneumonia

• Miscellaneous:

  • Fever
  • Head Trauma

Frequency of Side effects Not Defined:

• Cardiovascular:

  • Bradycardia
  • Cardiac Failure
  • Flushing
  • Hypertension
  • Orthostatic Hypotension
  • Palpitations
  • Syncope
  • Tachycardia

• Central Nervous System:

  • Aggressive Behavior
  • Apathy
  • Aphasia
  • Aura
  • Cerebral Hemorrhage
  • Delirium
  • Delusions
  • Dystonia
  • Euphoria Extrapyramidal Reaction
  • Hemiplegia
  • Hyperkinesia
  • Hyperreflexia
  • Hypertonia
  • Hypokinesia
  • Hyporeflexia
  • Hypotonia
  • Hysteria
  • Impaired Consciousness
  • Intoxicated Feeling
  • Malaise
  • Manic Behavior
  • Migraine
  • Neuralgia
  • Nightmares
  • Oculogyric Crisis
  • Panic Disorder
  • Paralysis
  • Paranoia
  • Personality Disorder
  • Precordial Pain
  • Psychomotor Retardation
  • Psychosis
  • Rigors
  • Speech Disturbance
  • Stupor
  • Voice Disorder

• Dermatologic:

  • Alopecia
  • Contact Dermatitis
  • Eczema
  • Erythematosus Rash
  • Facial Rash
  • Folliculitis
  • Genital Pruritus
  • Maculopapular Rash
  • Miliaria
  • Psoriasis
  • Skin Photosensitivity
  • Urticaria
  • Vitiligo

• Endocrine & Metabolic:

  • Change In Libido
  • Decreased T4
  • Heavy Menstrual Bleeding
  • Hyperglycemia
  • Hypocalcemia
  • Hypoglycemia
  • Hypokalemia
  • Increased Gamma-Glutamyl Transferase
  • Intermenstrual Bleeding
  • Weight Loss

• Gastrointestinal:

  • Aphthous Stomatitis
  • Biliary Colic
  • Bloody Stools
  • Cholelithiasis
  • Colitis
  • Duodenal Ulcer
  • Dysphagia
  • Enteritis
  • Eructation
  • Esophagitis
  • Flatulence
  • Gastric Ulcer
  • Gingival Hemorrhage
  • Gingival Hyperplasia
  • Hematemesis
  • Hemorrhoids
  • Hiccups
  • Increased Appetite
  • Retching
  • Sialadenitis
  • Stomatitis

• Genitourinary:

  • Dysuria
  • Hematuria
  • Leukorrhea
  • Priapism
  • Urinary Tract Pain

• Hematologic & Oncologic:

  • Thrombocytopenia

• Hepatic:

  • Increased Liver Enzymes

• Hypersensitivity:

  • Angioedema

• Neuromuscular & Skeletal:

  • Right Hypochondrium Pain
  • Systemic Lupus Erythematosus
  • Tetany

• Ophthalmic:

  • Blepharoptosis
  • Cataract
  • Conjunctival Hemorrhage
  • Hemianopia
  • Mydriasis
  • Ocular Edema
  • Photophobia
  • Scotoma
  • Xerophthalmia

• Otic:

  • Otitis Externa
  • Tinnitus

• Renal:

  • Nephrolithiasis
  • Polyuria
  • Renal Pain

• Respiratory:

  • Asthma
  • Dyspnea
  • Laryngismus
  • Pleurisy

Contraindications to Oxcarbazepine:

• Hypersensitivity to oxcarbazepine, and eslicarbazepine-acetate or any other component of the formulation.
• Limited documentation exists on the existence of allergenic cross-reactivity between carbamazepine analogs and carbamazepine.
• Cross-sensitivity can be possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Blood dyscrasias

  • Rarely, reports of agranulocytosis and leukopenia have been made about the use of this medication.
  • It may be necessary to discontinue treatment and convert to an alternate form of therapy.

• Bone disorders

  • The long-term effects of prolonged use have been linked to decreased bone mineral density and osteopenia.

• CNS effects

  • There have been reports of adverse effects in the CNS, including cognitive symptoms such as psychomotor slowing, difficulty concentrating, speech or language problems, somnolence, fatigue, coordination abnormalities and ataxia.
  • Patients should be cautious when performing tasks that require mental alertness, such as operating machinery or driving.

• Dermatologic reactions

  • There have been reports of potentially fatal and sometimes deadly dermatologic reactions in children and adults (eg, Stevens Johnson, toxic epidermal necrolysis).
  • The median time for onset was 19 days after treatment began.
  • Be aware of signs and symptoms that could indicate skin reactions. Alternate therapy may be necessary.
  • Oxcarbazepine has been associated with serious skin reactions that recurred.

• Hepatic dysfunction

  • Rarely has hepatitis been reported.
  • If you notice any signs of hepatic dysfunction, such as anorexia or nausea/vomiting, right-upper quadrant pain, pruritus, or other symptoms, immediately discontinue treatment.

• Hypersensitivity reactions

  • Rare cases of anaphylaxis or angioedema, even after initial dosing, have been reported. If symptoms persist, discontinue permanently.
  • Patients with a history of hypersensitivity to carbamazepine should be cautious. Cross-sensitivity can occur in 25 to 30% of patients.
  • In close association with the initiation of oxcarbazepine, potentially serious and sometimes fatal drug reactions with eosinophilia (DRESS), also known as multiorgan hypersensitivity reactions, have also been reported.
  • You should monitor for possible manifestations of lymphatic, hepatic and renal dysfunctions. Alternate therapy may be necessary.

• Hyponatremia

  • Clinically significant hyponatremia (serum salt 125 mmol/L), and syndrome of inappropriate antidiuretic hormonal hormone secretion may occur during treatment.
  • It usually occurs within the first three months of treatment, but it can occur up to one year later.
  • If hyponatremia symptoms occur (eg, nausea and malaise, headaches, lethargy or confusion, seizures), you should measure your serum sodium concentration.
  • Patients at high risk of hyponatremia should be monitored for serum sodium, particularly if they are elderly or taking medications that lower their sodium levels.
  • Hyponatremia patients may need to be given fluid restriction, dosage reduction or discontinuation of therapy.

• Hypothyroidism

  • Hypothyroidism has been documented; it is worth monitoring thyroid function, especially in children.
  • The return to normal thyroxine levels has been linked with discontinuing therapy.

• Suicidal thoughts:

  • A pooled analysis of antiepileptics trials (regardless if they were indicated) revealed an increase in suicidal thoughts/behavior. The incidence rate was 0.43% for patients treated, compared to 0.2% for patients who received placebo.
  • Risk can be observed as soon as one week after initiation, and continues throughout the trial (most trials last less than 24 weeks).
  • For any changes in behavior that could indicate depression or suicidal thoughts, monitor all patients.
  • If symptoms develop, patients should immediately notify their healthcare provider.

• Cardiovascular disease

  • Patients with severe cardiovascular disease or ECG abnormalities were not included in clinical trials.
  • Patients with HF should be monitored for body weight and fluid retention.
  • Assess serum sodium for signs of worsening cardiac function and fluid retention.

• Renal impairment

  • Single-dose studies have shown that patients with CrCl >30 mL/minute have a longer half-life.
  • These patients may require dose adjustment.

• Seizure disorder

  • Children have been known to experience exacerbation or new-onset primary generalized seizure, especially in the case of children.
  • Stop using oxcarbazepine in the event of seizure aggravation.

Oxcarbazepine: Drug Interaction

Risk Factor C (Monitor therapy)
Alcohol (Ethyl)	May enhance the CNS depressant effect of OXcarbazepine.
CloZAPine	CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine.
CYP3A4 Inducers (Strong)	May decrease the serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased.
Lacosamide	Antiepileptic Agents (Sodium Channel Blockers) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased.
LevETIRAcetam	OXcarbazepine may decrease the serum concentration of LevETIRAcetam.
Mianserin	May diminish the therapeutic effect of Anticonvulsants.
NiMODipine	CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine.
Orlistat	May decrease the serum concentration of Anticonvulsants.
RifAMPin	May decrease serum concentrations of the active metabolite(s) of OXcarbazepine. Specifically, concentrations of the major active 10-monohydroxy metabolite may be reduced.
Rivaroxaban	OXcarbazepine may decrease the serum concentration of Rivaroxaban.
Thiazide and Thiazide-Like Diuretics	May enhance the adverse/toxic effect of OXcarbazepine. Specifically, there may be an increased risk for hyponatremia.
Valproate Products	May decrease the serum concentration of OXcarbazepine.
Risk Factor D (Consider therapy modification)
Bictegravir	OXcarbazepine may decrease the serum concentration of Bictegravir. Management: When possible consider using an alternative anticonvulsant with concurrent bictegravir, emtricitabine, and tenofovir alafenamide. If the combination must be used, monitor closely for evidence of reduced antiviral effectiveness.
CarBAMazepine	May decrease serum concentrations of the active metabolite(s) of OXcarbazepine. Specifically, concentrations of the major active 10-monohydroxy metabolite may be reduced. Management: Consider increasing the initial adult oxcarbazepine extended release tablet (Oxtellar XR) dose to 900 mg/day. No specific recommendations are available for other oxcarbazepine formulations.
Cobicistat	OXcarbazepine may decrease the serum concentration of Cobicistat. Management: Consider an alternative antiepileptic when possible.
Estrogen Derivatives (Contraceptive)	OXcarbazepine may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal contraceptive is recommended.
Fosphenytoin-Phenytoin	May decrease serum concentrations of the active metabolite(s) of OXcarbazepine. Specifically, concentrations of the major active 10-monohydroxy metabolite may be reduced. OXcarbazepine may increase the serum concentration of Fosphenytoin-Phenytoin. Management: Consider increasing the initial adult oxcarbazepine extended release tablet (Oxtellar XR) dose to 900 mg/day. No specific recommendations are available for other oxcarbazepine formulations.
Mefloquine	May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use.
Perampanel	May increase the serum concentration of OXcarbazepine. OXcarbazepine may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used with oxcarbazepine. Patients receiving this combination should be followed closely for response, especially with any changes to oxcarbazepine therapy.
PHENobarbital	May decrease serum concentrations of the active metabolite(s) of OXcarbazepine. Specifically, concentrations of the major active 10-monohydroxy metabolite may be reduced. OXcarbazepine may increase the serum concentration of PHENobarbital. Management: Consider increasing the initial adult oxcarbazepine extended release tablet (Oxtellar XR) dose to 900 mg/day. No specific recommendations are available for other oxcarbazepine formulations.
Progestins (Contraceptive)	OXcarbazepine may decrease the serum concentration of Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an additional or alternative, nonhormonal method of contraception is recommended.
Risk Factor X (Avoid combination)
Dolutegravir	OXcarbazepine may decrease the serum concentration of Dolutegravir.
Doravirine	OXcarbazepine may decrease the serum concentration of Doravirine.
Elvitegravir	OXcarbazepine may decrease the serum concentration of Elvitegravir. Management: For elvitegravir plus a ritonavir-boosted protease inhibitor, use of oxcarbazepine is not recommended; for elvitegravir/cobicistat/emtricitabine/tenofovir combination products, consider using an alternative antiepileptic when possible.
Eslicarbazepine	May enhance the adverse/toxic effect of OXcarbazepine.
Ledipasvir	OXcarbazepine may decrease the serum concentration of Ledipasvir.
Rilpivirine	OXcarbazepine may decrease the serum concentration of Rilpivirine.
Selegiline	OXcarbazepine may enhance the serotonergic effect of Selegiline.
Simeprevir	OXcarbazepine may decrease the serum concentration of Simeprevir.
Sofosbuvir	OXcarbazepine may decrease the serum concentration of Sofosbuvir.
Tenofovir Alafenamide	OXcarbazepine may decrease the serum concentration of Tenofovir Alafenamide.
Ulipristal	OXcarbazepine may decrease the serum concentration of Ulipristal.

Monitoring Parameters:

• Seizure frequency.
• As needed (especially during the first three months of therapy), serum sodium.
• CNS depression symptoms (dizziness headaches somnolence)
• Hypersensitivity reactions.
• Patients who are taking other medications that lower sodium levels should have additional serum sodium monitoring.
• This is especially true for patients with hyponatremia signs and symptoms, as well as patients experiencing an increase in the severity or frequency of seizures.
• Periodic thyroid function testing (especially for children) and CBC.
• Suicidality monitoring (e.g. suicidal thoughts and depression, behavioral changes)
• As needed, serum levels of concomitant antiepileptic medications during titration.

How to administer Oxcarbazepine?

Immediate release:

• Administer twice a day without regard to meals.

Suspension:

• Prior to using it for the first time, firmly insert the plastic adapter provided with the bottle.
• Cover adapter with the child-resistant cap when not in use.
• Shake bottle for at least 10 seconds, remove the child-resistant cap and insert the oral dosing syringe provided to withdraw the appropriate dose.
• The dose may be taken directly from an oral syringe or may be mixed in a small glass of water immediately prior to swallowing.
• Rinse the syringe with warm water after use and allow to dry thoroughly.
• Discard any unused portion after 7 weeks of first opening the bottle.

Extended-release:

• Administer once a day on an empty stomach at least 1 hour before or 2 hours after food.
• Swallow whole; do not cut, crush, or chew the tablets.

Mechanism of action of Oxcarbazepine (Trileptal):

• Both oxcarbazepine (and its monohydroxy metabolite, MHD) have pharmacological activity.
• It is not known what the mechanism behind this anticonvulsant effect is.
• MHD and Oxcarbazepine block voltage-sensitive sodium channel voltage. They stabilize hyperexcited neuronal membranes and inhibit repetitive firing.
• This is believed to stop the spread of seizures.
• MHD and Oxcarbazepine also increase potassium conductance, and modulate activity of high-voltage activated Calcium channels.

Absorption:

• Complete

Protein binding:

• Oxcarbazepine: 67%; MHD: 40%, primarily to albumin; parent drug and metabolite do not bind to alpha-1 acid glycoprotein.

Metabolism:

• Oxcarbazepine is extensively metabolized in the liver to its active 10-monohydroxy metabolite (MHD).
• MHD undergoes further metabolism via glucuronide conjugation.
• 4% of the dose is oxidized to the 10,11-dihydroxy metabolite (DHD) (inactive); 70% of serum concentration appears as MHD, 2% as unchanged oxcarbazepine, and the rest as minor metabolites

Note: Unlike carbamazepine, autoinduction of metabolism has not been observed and biotransformation of oxcarbazepine does not result in an epoxide metabolite

Bioavailability:

• Immediate-release tablets and suspension have similar bioavailability (based on MDH serum concentrations).
• Extended-release tablets and immediate-release products are not bioequivalent.
• Immediate release: Decreased in children <8 years; increased in elderly >60 years

Half-life elimination:

• Children (Rey 2004): 2 to 5 years: MHD: Single dose: Mean range: 4.8 to 6.7 hours; 6 to 12 years: MHD: Single dose: Mean range: 7.2 to 9.3 hours
• Adults: Immediate release: Parent drug: 2 hours; MHD: 9 hours; renal impairment (CrCl 30 mL/minute): MHD: 19 hours.
• Extended-release: Parent drug: 7 to 11 hours; MHD: 9 to 11 hours

Time to peak serum concentration:

• Children 2 to 12 years: Immediate release: Oxcarbazepine: 1 hour; MHD: 3 to 4 hours (Rey 2004).
• Adults: Immediate release: MHD: Tablets: Median: 4.5 hours (range: 3 to 13 hours); Suspension: Median 6 hours.
• Extended-release: MHD: 7 hours

Excretion:

• Urine (95%, <1% as unchanged oxcarbazepine, 27% as unchanged MHD, 49% as MHD glucuronides, 3% as DHD (inactive), and 13% as a conjugate of oxcarbazepine and MHD);
• feces (<4%)
• Clearance (per body weight):
  • Children 2 to <4 years: Increased by ∼80% compared to adults
  • Children 4 to 12 years: Increased by ∼40% compared to adults
  • Children ≥13 years: Values approach adult clearance.

International Brand Names of Oxcarbazepine:

• Oxtellar XR
• Trileptal
• APO-OXcarbazepine
• JAMP-OXcarbazepine
• Trileptal
• Actinium
• Carbox
• Deprectal
• Leptal
• Lonazet
• Neurtrol
• Ocnobel
• Oleptal
• Oxalepsy
• Oxalept
• Oxazep
• Oxcar
• Oxetol
• Oxpin
• Oxrate
• Oxypine
• Prolepsi
• Sytoclon
• Timox
• Trileptal
• Trileptin

Oxcarbazepine Brand Names in Pakistan:

Oxcarbazepine Suspension 300 mg in Pakistan
Oxep	Macter International (Pvt) Ltd.

Oxcarbazepine Suspension 300 mg/5ml in Pakistan
Oxaze	Shrooq Pharmaceuticals

Oxcarbazepine 150 mg Tablets in Pakistan
Oxalepsy	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Oxaze	Shrooq Pharmaceuticals
Oxep	Macter International (Pvt) Ltd.
Oxzepin	Nabiqasim Industries (Pvt) Ltd.
Telox	Platinum Pharmaceuticals (Pvt.) Ltd.

Oxcarbazepine 300 mg Tablets in Pakistan
Oxalepsy	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Oxatep	Pakistan Pharmaceutical Products (Pvt) Ltd.
Oxaze	Shrooq Pharmaceuticals
Oxep	Macter International (Pvt) Ltd.
Oxzepin	Nabiqasim Industries (Pvt) Ltd.
Telox	Platinum Pharmaceuticals (Pvt.) Ltd.
Trioptal	Novartis Pharma (Pak) Ltd

Oxcarbazepine 600 mg Tablets in Pakistan
Oxalepsy	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Oxatep	Pakistan Pharmaceutical Products (Pvt) Ltd.
Oxaze	Shrooq Pharmaceuticals
Oxep	Macter International (Pvt) Ltd.
Oxzepin	Nabiqasim Industries (Pvt) Ltd.
Telox	Platinum Pharmaceuticals (Pvt.) Ltd.
Trioptal	Novartis Pharma (Pak) Ltd