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  • CLASSES

    Carboxamide Anticonvulsants

    DEA CLASS

    Rx

    DESCRIPTION

    Oral anticonvulsant that is a keto-analog of carbamazepine (CBZ); does not require routine drug concentration monitoring
    Indicated for partial seizures in adults and pediatric patients 2 years and older; used off-label for neuropathic pain in adults
    Close monitoring for emerging or worsening suicidal thoughts/behavior or depression recommended

    COMMON BRAND NAMES

    Oxtellar XR, Trileptal

    HOW SUPPLIED

    Oxcarbazepine/Trileptal Oral Susp: 5mL, 300mg
    Oxcarbazepine/Trileptal Oral Tab: 150mg, 300mg, 600mg
    Oxtellar XR Oral Tab ER: 150mg, 300mg, 600mg

    DOSAGE & INDICATIONS

    For the treatment of partial seizures.
    For monotherapy treatment of partial-onset seizures.
    Oral dosage (immediate-release tablets or oral suspension; e.g., Trileptal)
    Adults and Adolescents 17 years and older

    Initiate at 300 mg PO twice daily. Titrate by 300 mg/day every third day or 600 mg/day every week as indicated and tolerated. Max: 2,400 mg/day, given in 2 divided doses. Some data indicate that 1,200 mg/day may be effective in anticonvulsant-naive patients. When converting to oxcarbazepine from other anticonvulsants, initiate at 300 mg PO twice daily while beginning to reduce the dose of other anticonvulsants. Oxcarbazepine should be titrated upward by 600 mg/day every week over 2 to 4 weeks to achieve the recommended dose of 2,400 mg/day. The dosage(s) of concurrent anticonvulsants should be completely withdrawn over 3 to 6 weeks as tolerated. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. DISCONTINUATION: When discontinuing oxcarbazepine, withdraw oxcarbazepine gradually to minimize the potential for increased seizure frequency.

    Children and Adolescents 4 to 16 years

    Initiate at 8 to 10 mg/kg/day PO given in 2 divided doses. Increase the dose by 5 mg/kg/day every third day to the recommended weight-based daily maintenance dosage as follows: 600 to 900 mg/day PO for those 20 to 24.9 kg; give 900 to 1,200 mg/day PO for those 25 to 34.9 kg; 900 to 1,500 mg/day PO for those 35 to 44.9 kg; 1,200 to 1,500 mg/day PO for those 45 to 49.9 kg; 1,200 to 1,800 mg/day PO for those 50 to 59.9 kg; 1,200 to 2,100 mg/day PO for those 60 to 69.9 kg; and 1,500 to 2,100 mg/day PO for those 70 kg or more. When converting to oxcarbazepine monotherapy from other anticonvulsants, initiate at 8 to 10 mg/kg/day PO given in 2 divided doses while beginning to reduce the dose of the other antiepileptic drug. Observe the patient closely and taper the other antiepileptic drugs over a 3 to 6 week period while increasing the oxcarbazepine dosage in increments no greater than 10 mg/kg/day at weekly intervals to achieve the recommended daily monotherapy dose. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. DISCONTINUATION: When discontinuing oxcarbazepine, withdraw oxcarbazepine gradually to minimize the potential for increased seizure frequency.

    Oral dosage (extended-release tablets; e.g., Oxtellar XR)
    Adults and Adolescents 17 years and older

    Initiate at 600 mg PO once daily for 1 week. Increase dose weekly in 600 mg/day increments to achieve the recommended dose of 1,200 to 2,400 mg once daily. GERIATRIC PATIENTS: Initiate at 300 to 450 mg once daily and increase the dose slowly. Max: 2,400 mg/day PO. The 2,400 mg/day dose showed slightly greater efficacy than 1,200 mg/day during clinical trials, but was associated with an increase in adverse reactions. The extended-release (ER) tablets are not bioequivalent to the same total daily dose of the immediate-release formulation; higher doses of the ER tablet may be necessary. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. DISCONTINUATION: When discontinuing oxcarbazepine, withdraw oxcarbazepine gradually to minimize the potential for increased seizure frequency.

    Children and Adolescents 6 to 16 years

    Initiate at 8 to 10 mg/kg PO once daily (do not exceed 600 mg PO once daily) in the first week. Increase dose weekly in 8 to 10 mg/kg/day increments (not to exceed 600 mg/day per week) to achieve the recommended weight-based maintenance dosage as follows: 900 mg/day for those 20 to 29 kg; 1,200 mg/day for those 29.1 to 39 kg; and 1,800 mg/day for those greater than 39 kg. When converting from immediate-release formulations to the extended-release (ER) tablet, higher doses of the ER tablet may be necessary. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. DISCONTINUATION: When discontinuing oxcarbazepine, withdraw oxcarbazepine gradually to minimize the potential for increased seizure frequency.

    For adjunct treatment of partial-onset seizures.
    Oral dosage (immediate-release tablets or oral suspension; e.g., Trileptal)
    Adults and Adolescents 17 years and older

    Initiate at 300 mg PO twice daily. May increase by no more than 600 mg/day at weekly intervals up to 1,200 mg/day, given in 2 divided doses. Dosages greater than 1,200 mg/day are considered more effective; however, in a large clinical trial, 65% of subjects withdrew from the study because of intolerable CNS effects from combined anticonvulsant therapy. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. DISCONTINUATION: When discontinuing oxcarbazepine, withdraw oxcarbazepine gradually to minimize the potential for increased seizure frequency.

    Children and Adolescents 2 to 16 years

    Initiate at 8 to 10 mg/kg/day PO (generally 600 mg/day or less), given in 2 divided doses. For patients less than 20 kg, consider a starting dose of 16 to 20 mg/kg/day PO. The target dose should be achieved over 2 to 4 weeks. Individualize dosage. Suggested target maintenance dose for children 2 to less than 4 years of age: 60 mg/kg/day PO. Suggested target maintenance doses for children 4 to 16 years are weight-based: 900 mg/day PO for those 20 to 29 kg; 1,200 mg/day PO for those 29.1 to 39 kg; 1,800 mg/day PO for those greater than 39 kg. In clinical trials, the median daily dose was 31 mg/kg (range 6 to 51 mg/kg) in children aged 4 to 16 years, while 50% of children aged 2 to younger than 4 years reached a final daily dose of 55 mg/kg (with 60 mg/kg/day being the target dose). ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. DISCONTINUATION: When discontinuing oxcarbazepine, withdraw oxcarbazepine gradually to minimize the potential for increased seizure frequency.

    Oral dosage (extended-release tablets; e.g., Oxtellar XR)
    Adults and Adolescents 17 years and older

    Initiate at 600 mg PO once daily for 1 week. Increase dose weekly in 600 mg/day increments to achieve the recommended dose of 1,200 to 2,400 mg once daily. GERIATRIC PATIENTS: Initiate at 300 to 450 mg once daily and increase the dose slowly. Max: 2,400 mg/day PO. When converting from immediate-release formulations to the extended-release (ER) tablet, higher doses of the ER tablet may be necessary; specific recommendations are not provided. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. DISCONTINUATION: When discontinuing oxcarbazepine, withdraw oxcarbazepine gradually to minimize the potential for increased seizure frequency.

    Children and Adolescents 6 to 16 years

    Initiate at 8 to 10 mg/kg PO once daily (do not exceed 600 mg PO once daily) in the first week. Increase dose weekly in 8 to 10 mg/kg/day increments (not to exceed 600 mg/day per week) to achieve the recommended weight-based maintenance dosage as follows: 900 mg/day for those 20 to 29 kg; 1,200 mg/day for those 29.1 to 39 kg; and 1,800 mg/day for those greater than 39 kg. When converting from immediate-release formulations to the extended-release (ER) tablet, higher doses of the ER tablet may be necessary; specific recommendations are not provided. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. DISCONTINUATION: When discontinuing oxcarbazepine, withdraw oxcarbazepine gradually to minimize the potential for increased seizure frequency.

    For the treatment of trigeminal neuralgia†.
    Oral dosage (immediate-release tablets or oral suspension)
    Adults

    Initialy, 300 mg PO twice daily. Titrate as tolerated to effect, using recommended dosage titration schedules. May be increased by no more than 600 mg/day at weekly intervals. Most patients respond to doses between 900—2400 mg/day PO.

    For the treatment of mania† associated with bipolar disorder†.
    For the treatment of mania† associated with bipolar disorder† in adults.
    Oral dosage (immediate-release tablets or oral suspension)
    Adults

    Dosage and efficacy not established. There are insufficient trials of adequate quality to be informative. If treatment is considered clinically necessary, initiate with 300 mg PO twice daily. Increase by 300 mg/day at a minimum of every 2 days as tolerated to an effective dose. Max: 2,400 mg/day PO, given in divided doses. Some small pilot trials in adults indicate potential efficacy. In a small study, the mean daily dose was 1,280 mg/day (range: 1,000 mg to 2,400 mg/day), given in divided doses. Oxcarbazepine is a third-line monotherapy off-label treatment option for manic or mixed episodes per the Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines; the drug is also third line as a maintenance or adjunctive treatment. The Texas Medication Algorithm Project procedural manual for bipolar disorder considers oxcarbazepine a Stage III adjunct treatment option for patients with partial or non-response to first and second-line medication regimens. The NICE U.K. guidelines do not include oxcarbazepine in the treatment algorithms for bipolar disorder.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    2,400 mg/day PO.

    Geriatric

    2,400 mg/day PO.

    Adolescents

    17 years: 2,400 mg/day PO of immediate-release formulations; see individualized age and weight-dependent dosage recommendations for the extended-release tablets.
    13 to 16 years: See individualized age and weight-dependent dosage recommendations.

    Children

    6 to 12 years: See individualized age and weight-dependent dosage recommendations.
    4 to 5 years: See individualized age and weight-dependent dosage recommendations for immediate-release formulations; safety and efficacy of the extended-release tablets not established.
    2 to 3 years: 60 mg/kg/day PO (in 2 divided doses) of immediate-release formulations; safety and efficacy of the extended-release tablets not established.
    Less than 2 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustments recommended for mild to moderate hepatic impairment. The effects of severe hepatic impairment have not been evaluated. Caution is recommended when using immediate-release formulations in patients with severe hepatic impairment; use of extended-release tablets in patients with severe hepatic impairment is not recommended.

    Renal Impairment

    CrCl >= 30 ml/min: No dosage adjustments have been recommended, but renal clearance of MHD, the active metabolite, declines linearly with a decrease in creatinine clearance.
    CrCl < 30 ml/min: Renal clearance of MHD, the active metabolite, is prolonged to 19 hours; therefore, initiate therapy with 50% of the usual starting dose and slowly titrate upward. For the extended-release tablets, subsequent dose increases can occur at weekly intervals in 300—450 mg/day increments.
     
    Dialysis
    The manufacturer of extended-release tablets recommends using the immediate-release formulations in patients on dialysis.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Extended-release tablets
    Take on an empty stomach at least 1 hour before or 2 hours after meals. If the tablet is taken with food, adverse reactions are more likely to occur.
    Swallow tablet whole. Do not cut, crush, or chew the tablet.
     
    Immediate-release tablets
    May be taken with or without food.

    Oral Liquid Formulations

    Oral suspension:
    Shake well before each use.
    Prepare the dose just prior to administration.
    To ensure accurate dosage, only use the provided calibrated oral dosing syringe.
    Dosage may be mixed in a small glass of water prior to administration if desired. Alternatively, may be swallowed directly from the syringe.
    After each use, rinse the syringe with warm water and allow it to dry thoroughly.
    Discard any unused medication after 7 weeks of first opening the bottle.

    STORAGE

    Oxtellar XR:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Trileptal:
    - Do not freeze
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Abrupt discontinuation

    In general, abrupt discontinuation of anticonvulsants may precipitate rebound seizures. Although this has not yet been documented with oxcarbazepine, withdrawal over several weeks is recommended if discontinuation is necessary.

    Asian patients, carbamazepine hypersensitivity, serious rash

    Oxcarbazepine should not be used in patients with a known hypersensitivity reaction to the drug or any of its components. In rare instances, anaphylaxis and angioedema involving the larynx, glottis, lips, and eyelids have been reported following initial or subsequent dosing of oxcarbazepine. Oxcarbazepine may also cause life-threatening serious rash that may require hospitalization, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Patients who carry the HLA-B 1502 allele may be at increased risk for developing these serious adverse reactions with oxcarbazepine treatment. A strong association between SJS/TEN and the allele has been found in patients who took carbamazepine, which is structurally similar to oxcarbazepine. Approximately 25—30% of patients with carbamazepine hypersensitivity will react to oxcarbazepine. The risk of SJS/TEN is about 1 to 6 per 10,000 new users in countries with mainly Caucasian populations. However, other populations may be at greater risk. The risk of these reactions in countries with primarily Asian patients may be 10 times higher because of variants found in the immune system gene HLA-B 1502, which occur at a higher rate in Asian patients. Consider testing for the presence of HLA-B 1502 in genetically at-risk patients. In patients positive for HLA-B 1502, oxcarbazepine should be avoided unless the benefits of treatment significantly outweigh the risks. The test does not appear to be beneficial in those who have been taking oxcarbazepine for more than a few months, since it is unlikely that the skin reactions will develop after that time regardless of the presence or absence of the variant gene. Patients should be made aware of the early signs and symptoms of potential hematological, dermatological, hypersensitivity or hepatic reactions. The patient should be advised to report any such occurrences immediately to a physician. The patient should be advised that these signs and symptoms should be reported even if mild or occurring after extended use. The median time of onset for reported cases was 19 days. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or multi-organ hypersensitivity reactions have occurred in close temporal association (median time 13 days: range 4—60) to the start of oxcarbazepine therapy in adult and pediatric patients. Patients typically present with fever, rash and/or lymphadenopathy associated with other organ system involvement. Eosinophilia may be present. If a hypersensitivity or serious skin or organ reaction is suspected, oxcarbazepine should be discontinued permanently and an alternative treatment started.

    Depression, suicidal ideation

    In January 2008, the FDA alerted healthcare professionals of an increased risk of suicidal ideation and behavior in patients receiving anticonvulsants to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). This alert followed an initial request by the FDA in March 2005 for manufacturers of marketed anticonvulsants to provide data from existing controlled clinical trials for analysis. Prior to this request, preliminary evidence had suggested a possible link between anticonvulsant use and suicidality. The primary analysis consisted of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (>= 5 years of age). There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation as patients receiving placebo (0.43% vs. 0.24%, respectively; RR 1.8, 95% CI: 1.2—2.7). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions; however, the absolute risk differences were similar in trials for epilepsy and psychiatric indications. Age was not a determining factor. The increased risk of suicidal ideation and behavior was observed between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. Data were analyzed from drugs with adequately designed clinical trials including carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide. However, this is considered to be a class effect. All patients beginning treatment with anticonvulsants or currently receiving such treatment should be closely monitored for emerging or worsening depression or suicidal thoughts/behavior. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. Anticonvulsants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.

    Hyponatremia

    Clinically significant hyponatremia (sodium < 125 mmol/L) may develop during treatment with oxcarbazepine. This typically occurs during the first 3 months; however, cases of symptomatic hyponatremia beginning more than 1 year after treatment initiation have been observed. Normalization of sodium levels usually occurs within a few days of discontinuing the drug. Monitoring of sodium levels should be considered if oxcarbazepine is used with other medications known to decrease sodium levels, in those with baseline hyponatremia, or if symptoms possibly indicating hyponatremia develop (e.g., nausea, malaise, headache, lethargy, confusion, obtundation, or increase in seizure frequency or severity).

    Renal failure, renal impairment

    Oxcarbazepine should be used cautiously in those with renal impairment or renal failure as the primary route of oxcarbazepine metabolite elimination is via the kidneys. The elimination half-life of MHD is prolonged when the creatinine clearance falls below 30 ml/min; therefore, dosage adjustments are recommended (see Dosage).

    Driving or operating machinery

    Advise patients to avoid driving or operating machinery until they have gained sufficient experience on oxcarbazepine to gauge whether it adversely affects their ability to drive or operate machinery. Oxcarbazepine may cause dizziness, somnolence, ataxia, visual disturbances, and depressed level of consciousness.

    Geriatric

    There were 52 geriatric patients greater than 65 years of age in controlled clinical trials of oxcarbazepine and 565 patients more than 65 years of age in other trials. Single and multiple dose studies of oxcarbazepine indicate that the maximum plasma concentrations and AUC values of MHD, the active metabolite, are 30% to 60% higher in geriatric patients. This increase has been attributed to the decline in creatinine clearance (CrCl) associated with age. Lower initial doses may be necessary in the geriatric patients based on the degree of renal impairment. The manufacturer recommends dose adjustments and slower titration for any patient with CrCl less than 30 mL/minute, regardless of age. According to the Beers Criteria, anticonvulsants are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, with the exception of treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If oxcarbazepine must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. Lastly, the Panel recommends using oxcarbazepine cautiously in older adults because oxcarbazepine can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions. Sodium levels should be closely monitored when starting or changing dosages in older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, some anticonvulsants may be used to treat disorders other than seizures (e.g., bipolar disorder, schizoaffective disorder, chronic neuropathic pain, migraine prevention). The need for indefinite continuation in treating any condition should be based on confirmation of the condition and its potential cause(s). Determining effectiveness and tolerability through evaluation of symptoms should be used to adjust doses. Therapeutic drug monitoring is not required or available for most anticonvulsants. In addition, significant signs and symptoms of toxicity can occur at normal or low serum concentrations, and symptom control for seizures or behavior can occur at subtherapeutic serum concentrations. Obtaining serum medication concentrations may assist in identifying toxicity. High or toxic serum concentrations should become a consideration for dosage adjustments. Anticonvulsants may cause liver dysfunction, blood dyscrasias, and serious skin rashes requiring treatment discontinuation. Anticonvulsants may also cause nausea/vomiting, dizziness, ataxia, somnolence/lethargy, incoordination, blurred or double vision, restlessness, toxic encephalopathy, anorexia, and headaches; these effects can increase the risk for falls. When an anticonvulsant is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity in accordance with OBRA guidelines.

    Pregnancy

    There are no adequate data on the developmental risk associated with oxcarbazepine use during human pregnancy. Data from pregnancy registries suggest that oxcarbazepine monotherapy is associated with craniofacial defects such as oral clefts and cardiac malformations such as ventricular septal defects. An increase in seizure frequency may occur during pregnancy due to altered concentrations of the active metabolite of oxcarbazepine. Monitor patients carefully during pregnancy and the postpartum period. Oxcarbazepine is structurally related to carbamazepine, which is considered to be teratogenic in humans. Increased incidences of fetal structural abnormalities, embryolethality, and growth retardation were observed in offspring of animals treated with oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at exposures similar to the maximum recommended human dose. Encourage women taking oxcarbazepine during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.[29014]

    Breast-feeding

    Oxcarbazepine and its active metabolite (MHD) are excreted in human breast milk. The effects of oxcarbazepine and its active metabolite on the breast-fed infant or on milk production are unknown.[29014] Milk to plasma ratios of 0.5 and 0.5 to 0.8 for oxcarbazepine and MHD, respectively, have been reported. Based on concentrations of oxcarbazepine in the breast milk of 1 mother taking 600 mg/day (weight-corrected dose of 9 mg/kg), it was estimated that an exclusively breast-fed infant with an average milk ingestion of 0.15 L/kg per day would receive approximately 1.5% to 1.7% of the maternal weight-adjusted dose. Infant plasma concentrations of oxcarbazepine and its metabolite on days 8 and 23 postpartum were less than 0.1 to 0.2 mcg/mL. The infant was breast fed for a total of 18 weeks; no adverse events or developmental delays were observed up to 5 years of age.[46392] Previous American Academy of Pediatrics (AAP) recommendations considered carbamazepine to be usually compatible with breast-feeding; however, the AAP did not evaluate oxcarbazepine.[27500] Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for oxcarbazepine and any potential adverse effects on the breast-fed infant from oxcarbazepine or the underlying maternal condition.[29014]

    ADVERSE REACTIONS

    Severe

    visual impairment / Early / 4.0-14.0
    hyponatremia / Delayed / 1.2-2.5
    suicidal ideation / Delayed / 0-1.0
    muscle paralysis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    hematemesis / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    water intoxication / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    bone fractures / Delayed / Incidence not known
    ocular hemorrhage / Delayed / Incidence not known
    heart failure / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    pancytopenia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    teratogenesis / Delayed / Incidence not known

    Moderate

    ataxia / Delayed / 5.0-7.0
    confusion / Early / 7.0-7.0
    amnesia / Delayed / 4.0-5.0
    constipation / Delayed / 5.0-5.0
    hematoma / Early / 4.0-4.0
    blurred vision / Early / 1.0-4.0
    gastritis / Delayed / 0-3.0
    nystagmus / Delayed / 2.0-2.0
    dysarthria / Delayed / 2.0-2.0
    EEG changes / Delayed / 0-2.0
    hot flashes / Early / 2.0-2.0
    chest pain (unspecified) / Early / 2.0-2.0
    edema / Delayed / 2.0-2.0
    peripheral edema / Delayed / 1.0-2.0
    myasthenia / Delayed / 1.0-2.0
    hypotension / Rapid / 0-2.0
    vaginitis / Delayed / 2.0-2.0
    lymphadenopathy / Delayed / 2.0-2.0
    dystonic reaction / Delayed / Incidence not known
    tetany / Early / Incidence not known
    aphasia / Delayed / Incidence not known
    dysphonia / Delayed / Incidence not known
    myoclonia / Delayed / Incidence not known
    impaired cognition / Early / Incidence not known
    migraine / Early / Incidence not known
    hyperreflexia / Delayed / Incidence not known
    hypotonia / Delayed / Incidence not known
    delirium / Early / Incidence not known
    psychosis / Early / Incidence not known
    depression / Delayed / Incidence not known
    mania / Early / Incidence not known
    euphoria / Early / Incidence not known
    esophagitis / Delayed / Incidence not known
    cholelithiasis / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    gingival hyperplasia / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    hemorrhoids / Delayed / Incidence not known
    melena / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    psoriasis / Delayed / Incidence not known
    atopic dermatitis / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    hypertonia / Delayed / Incidence not known
    osteoporosis / Delayed / Incidence not known
    cataracts / Delayed / Incidence not known
    photophobia / Early / Incidence not known
    ocular inflammation / Early / Incidence not known
    scotomata / Delayed / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    palpitations / Early / Incidence not known
    dysuria / Early / Incidence not known
    priapism / Early / Incidence not known
    hematuria / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hyperamylasemia / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    hypothyroidism / Delayed / Incidence not known

    Mild

    headache / Early / 13.0-31.0
    dizziness / Early / 22.0-28.0
    nausea / Early / 16.0-22.0
    fatigue / Early / 21.0-21.0
    drowsiness / Early / 19.0-19.0
    vomiting / Early / 7.0-15.0
    diplopia / Early / 12.0-12.0
    infection / Delayed / 2.0-10.0
    rhinitis / Early / 2.0-10.0
    emotional lability / Early / 3.0-8.0
    anxiety / Delayed / 7.0-7.0
    diarrhea / Early / 7.0-7.0
    asthenia / Delayed / 2.0-7.0
    tremor / Early / 4.0-6.0
    insomnia / Early / 6.0-6.0
    dyspepsia / Early / 5.0-6.0
    abdominal pain / Early / 5.0-5.0
    anorexia / Delayed / 5.0-5.0
    cough / Delayed / 5.0-5.0
    dysgeusia / Early / 5.0-5.0
    sinusitis / Delayed / 4.0-4.0
    epistaxis / Delayed / 4.0-4.0
    back pain / Delayed / 4.0-4.0
    hypoesthesia / Delayed / 3.0-3.0
    xerostomia / Early / 3.0-3.0
    hyperhidrosis / Delayed / 3.0-3.0
    fever / Early / 3.0-3.0
    pharyngitis / Delayed / 3.0-3.0
    dental pain / Delayed / 2.0-2.0
    weight gain / Delayed / 1.0-2.0
    rash / Early / 2.0-2.0
    purpura / Delayed / 2.0-2.0
    acne vulgaris / Delayed / 1.0-2.0
    otalgia / Early / 2.0-2.0
    increased urinary frequency / Early / 2.0-2.0
    hyporeflexia / Delayed / Incidence not known
    hyperkinesis / Delayed / Incidence not known
    ptosis / Delayed / Incidence not known
    libido increase / Delayed / Incidence not known
    libido decrease / Delayed / Incidence not known
    agitation / Early / Incidence not known
    hiccups / Early / Incidence not known
    eructation / Early / Incidence not known
    gingivitis / Delayed / Incidence not known
    appetite stimulation / Delayed / Incidence not known
    weight loss / Delayed / Incidence not known
    flatulence / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    flushing / Rapid / Incidence not known
    folliculitis / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    maculopapular rash / Early / Incidence not known
    malaise / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    xerophthalmia / Early / Incidence not known
    vertigo / Early / Incidence not known
    mydriasis / Early / Incidence not known
    syncope / Early / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    menorrhagia / Delayed / Incidence not known
    leukorrhea / Delayed / Incidence not known
    polyuria / Early / Incidence not known
    polydipsia / Early / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Major) Avoid concurrent use of dolutegravir with oxcarbazepine, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Oxcarbazepine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with oxcarbazepine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If oxcarbazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Oxcarbazepine is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of oxycodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Alfentanil: (Moderate) Drugs that induce cytochrome P450 3A4, including oxcarbazepine, may decrease the effectiveness of alfentanil. Alfentanil is a substrate for the cytochrome 3A4 isoenzyme. Induction of alfentanil metabolism may take several days.
    Aliskiren; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Alprazolam: (Moderate) Oxcarbazepine and its active metabolite, MHD, are dose-dependent inducers of the hepatic CYP3A4/5 isoenzymes thereby having the potential to lower the plasma levels of medications metabolized through these pathways. The effectiveness of medications such as alprazolam could theoretically be decreased. In addition, concomitant administration of alprazolam with CNS-depressant drugs, including anticonvulsants, can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Amitriptyline: (Moderate) Use amitriptyline with caution in patients with a history of seizures; amitriptyline may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of amitriptyline and oxcarbazepine may result in additive CNS depression. Oxcarbazepine, a CYP2C19 inhibitor, can increase plasma concentrations of amitriptyline, a substrate of CYP2C19.
    Amitriptyline; Chlordiazepoxide: (Moderate) Use amitriptyline with caution in patients with a history of seizures; amitriptyline may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of amitriptyline and oxcarbazepine may result in additive CNS depression. Oxcarbazepine, a CYP2C19 inhibitor, can increase plasma concentrations of amitriptyline, a substrate of CYP2C19.
    Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Amlodipine; Atorvastatin: (Moderate) Monitor for potential reduced cholesterol-lowering efficacy when oxcarbazepine is coadministered with atorvastatin. Oxcarbazepine, which is a CYP3A4 inducer, may decrease the efficacy of atorvastatin, a CYP3A4 substrate. (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Amlodipine; Benazepril: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Amlodipine; Olmesartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Amlodipine; Telmisartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Amlodipine; Valsartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Coadministration of oxcarbazepine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of oxcarbazepine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
    Aripiprazole: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during use of a CYP3A4 inducer such as oxcarbazepine. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. A dose adjustment of aripiprazole may be needed. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Artemether; Lumefantrine: (Major) Oxcarbazepine is an inducer and both components of artemether; lumefantrine are substrates of the CYP3A4 isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations. Concomitant use warrants caution due to a possible reduction in antimalarial activity.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with oxcarbazepine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If oxcarbazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Oxcarbazepine is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Aspirin, ASA; Carisoprodol: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as oxcarbazepine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as oxcarbazepine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
    Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of oxycodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Atazanavir: (Major) Oxcarbazepine may increase the metabolism of atazanavir and lead to decreased antiretroviral efficacy. Treatment failures have been reported with other protease inhibitors when carbamazepine was used concomitantly. If atazanavir is added to anticonvulsant therapy, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or seizure control. Monitor serum concentrations.
    Atazanavir; Cobicistat: (Major) Coadministration of oxcarbazepine with regimens containing cobicistat and atazanavir or darunavir should be avoided. If these drugs are used together, significant decreases in the plasma concentrations of cobicistat, atazanavir and potentally darunavir may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Oxcarbazepine may increase the metabolism of atazanavir and lead to decreased antiretroviral efficacy. Treatment failures have been reported with other protease inhibitors when carbamazepine was used concomitantly. If atazanavir is added to anticonvulsant therapy, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or seizure control. Monitor serum concentrations.
    Atorvastatin: (Moderate) Monitor for potential reduced cholesterol-lowering efficacy when oxcarbazepine is coadministered with atorvastatin. Oxcarbazepine, which is a CYP3A4 inducer, may decrease the efficacy of atorvastatin, a CYP3A4 substrate.
    Atorvastatin; Ezetimibe: (Moderate) Monitor for potential reduced cholesterol-lowering efficacy when oxcarbazepine is coadministered with atorvastatin. Oxcarbazepine, which is a CYP3A4 inducer, may decrease the efficacy of atorvastatin, a CYP3A4 substrate.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if phenobarbital and oxcarbazepine are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of phenobarbital. Additive CNS depression may also occur. Coadministration of oxcarbazepine (600 to 1,800 mg/day) with phenobarbital (100 to 150 mg/day) decreased the plasma concentration of MHD by 25% and increased the plasma concentration of phenobarbital by 14%. Strong CYP3A4 inducers and UGT inducers have been shown to decrease plasma concentrations of MHD. Phenobarbital is a strong CYP3A4 inducer and UGT inducer.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if phenobarbital and oxcarbazepine are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of phenobarbital. Additive CNS depression may also occur. Coadministration of oxcarbazepine (600 to 1,800 mg/day) with phenobarbital (100 to 150 mg/day) decreased the plasma concentration of MHD by 25% and increased the plasma concentration of phenobarbital by 14%. Strong CYP3A4 inducers and UGT inducers have been shown to decrease plasma concentrations of MHD. Phenobarbital is a strong CYP3A4 inducer and UGT inducer.
    Brexpiprazole: (Moderate) Because brexpiprazole is partially metabolized by CYP3A4, systemic exposure to brexpiprazole may be decreased during co-administration of a CYP3A4 inducer, such as oxcarbazepine. If these agents are used in combination, the patient should be carefully monitored for a decrease in brexpiprazole efficacy and dose adjustments made accordingly.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Buprenorphine: (Moderate) Close monitoring of the patient is recommended if a CYP3A4 inducer, such as oxcarbazepine, is used with a CYP3A4 substrate, such as buprenorphine. Moderate to strong CYP3A4 inducers may increase the hepatic metabolism of buprenorphine, which may lead to opiate withdrawal or inadequate pain control. This interaction is most significant if the enzyme-inducing agent is added after buprenorphine therapy has begun. Buprenorphine doses may need to be increased if a CYP3A4 inducer is added. Conversely, buprenorphine doses may need to be decreased if the CYP3A4 inducer discontinued.
    Buprenorphine; Naloxone: (Moderate) Close monitoring of the patient is recommended if a CYP3A4 inducer, such as oxcarbazepine, is used with a CYP3A4 substrate, such as buprenorphine. Moderate to strong CYP3A4 inducers may increase the hepatic metabolism of buprenorphine, which may lead to opiate withdrawal or inadequate pain control. This interaction is most significant if the enzyme-inducing agent is added after buprenorphine therapy has begun. Buprenorphine doses may need to be increased if a CYP3A4 inducer is added. Conversely, buprenorphine doses may need to be decreased if the CYP3A4 inducer discontinued.
    Bupropion: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as carbamazepine, barbiturates, or phenytoin, as well as fosphenytoin and ethotoin.
    Bupropion; Naltrexone: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as carbamazepine, barbiturates, or phenytoin, as well as fosphenytoin and ethotoin.
    Carbamazepine: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if carbamazepine and oxcarbazepine are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of carbamazepine. Coadministration of carbamazepine (400 to 2,000 mg/day) with oxcarbazepine (900 mg/day) decreased MHD concentrations by 40%. Strong CYP3A4 inducers or UGT inducers have been shown to decrease plasma concentrations of MHD. Carbamazepine is a strong CYP3A4 inducer and a UGT inducer.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as oxcarbazepine, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear.
    Carisoprodol: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as oxcarbazepine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with oxcarbazepine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If oxcarbazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Oxcarbazepine is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with oxcarbazepine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If oxcarbazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Oxcarbazepine is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Cisapride: (Moderate) Cisapride is metabolized by the hepatic cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme. Inducers of CYP3A4, such as oxcarbazepine, may increase the clearance of cisapride.
    Citalopram: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with oxcarbazepine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Clarithromycin: (Major) Coadministration of oxcarbazepine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
    Clomipramine: (Moderate) Use clomipramine with caution in patients with a history of seizures; clomipramine may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of clomipramine and oxcarbazepine may result in additive CNS depression. Oxcarbazepine, a CYP2C19 inhibitor, can increase plasma concentrations of clomipramine, a substrate of CYP2C19.
    Clopidogrel: (Major) Oxcarbazepine may reduce the antiplatelet activity of clopidogrel by inhibiting clopidogrel's metabolism to its active metabolite. Use oxcarbazepine and clopidogrel together with caution and monitor for reduced efficacy of clopidogrel. Clopidogrel requires hepatic biotransformation via 2 cytochrome dependent oxidative steps; the CYP2C19 isoenzyme is involved in both steps. Oxcarbazepine is an inhibitor of CYP2C19.
    Clozapine: (Major) Clozapine has an established risk of seizures, which may compromise the effectiveness of oxcarbazepine in the treatment of seizure disorders. In addition, concurrent use of clozapine and oxcarbazepine may decrease the therapeutic effects of clozapine since oxcarbazepine is an inducer of CYP3A4 and clozapine is a substrate for this isoenzyme. According to the manufacturer of clozapine, patients receiving clozapine in combination with a weak to moderate CYP3A4 inducer should be monitored for loss of effectiveness. Consideration should be given to increasing the clozapine dose if necessary. If the inducer is discontinued, monitor for adverse reactions, and consider reducing the clozapine dose if necessary. Monitor for additive CNS effects.
    Cobicistat: (Major) Coadministration of oxcarbazepine with regimens containing cobicistat and atazanavir or darunavir should be avoided. If these drugs are used together, significant decreases in the plasma concentrations of cobicistat, atazanavir and potentally darunavir may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. Consider use of an alternative anticonvulsant or antiretroviral therapy.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Oxcarbazepine induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with oxcarbazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased. (Major) Coadministration of oxcarbazepine with regimens containing cobicistat and atazanavir or darunavir should be avoided. If these drugs are used together, significant decreases in the plasma concentrations of cobicistat, atazanavir and potentally darunavir may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. Consider use of an alternative anticonvulsant or antiretroviral therapy.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Oxcarbazepine induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with oxcarbazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased. (Major) Coadministration of oxcarbazepine with regimens containing cobicistat and atazanavir or darunavir should be avoided. If these drugs are used together, significant decreases in the plasma concentrations of cobicistat, atazanavir and potentally darunavir may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. Consider use of an alternative anticonvulsant or antiretroviral therapy.
    Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of oxcarbazepine. To minimize potential for interactions, consider administering oral anticonvulsants such as oxcarbazepine at least 1 hour before or at least 4 hours after colesevelam.
    Conjugated Estrogens: (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Conjugated Estrogens; Bazedoxifene: (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Conjugated Estrogens; Medroxyprogesterone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Cyclosporine: (Moderate) Oxcarbazepine and its active metabolite, MHD, are dose-dependent inducers of the hepatic CYP3A4/5 isoenzymes thereby having the potential to lower the plasma levels of medications metabolized through these pathways, including cyclosporine.
    Darunavir: (Major) Oxcarbazepine may increase the metabolism of darunavir and lead to decreased antiretroviral efficacy. Treatment failures have been reported with other protease inhibitors when carbamazepine was used concomitantly. If darunavir is added to anticonvulsant therapy, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or seizure control. Monitor serum concentrations.
    Darunavir; Cobicistat: (Major) Coadministration of oxcarbazepine with regimens containing cobicistat and atazanavir or darunavir should be avoided. If these drugs are used together, significant decreases in the plasma concentrations of cobicistat, atazanavir and potentally darunavir may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Oxcarbazepine may increase the metabolism of darunavir and lead to decreased antiretroviral efficacy. Treatment failures have been reported with other protease inhibitors when carbamazepine was used concomitantly. If darunavir is added to anticonvulsant therapy, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or seizure control. Monitor serum concentrations.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of oxcarbazepine with regimens containing cobicistat and atazanavir or darunavir should be avoided. If these drugs are used together, significant decreases in the plasma concentrations of cobicistat, atazanavir and potentally darunavir may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Oxcarbazepine may increase the metabolism of darunavir and lead to decreased antiretroviral efficacy. Treatment failures have been reported with other protease inhibitors when carbamazepine was used concomitantly. If darunavir is added to anticonvulsant therapy, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or seizure control. Monitor serum concentrations.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Severe) Concurrent administration of oxcarbazepine with dasabuvir; ombitasvir; paritaprevir; ritonavir is contraindicated. Taking these drugs together could result in decreased plasma concentrations of paritaprevir, ritonavir, and dasabuvir, which may affect antiviral efficacy. Oxcarbazepine is a moderate inducer of the hepatic isoenzyme CYP3A4, and ritonavir, paritaprevir, and dasabuvir (minor) are CYP3A4 substrates. (Major) Concurrent administration of oxcarbazepine with ritonavir should be undertaken with caution and careful monitoring of antiviral efficacy. Oxcarbazepine is a moderate inducer of the hepatic isoenzyme CYP3A4, and ritonavir is a CYP3A4 substrate.
    Desipramine: (Moderate) Use desipramine with caution in patients with a history of seizures; desipramine may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of desipramine and oxcarbazepine may result in additive CNS depression.
    Dienogest; Estradiol valerate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Diethylstilbestrol, DES: (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with oxcarbazepine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If oxcarbazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Oxcarbazepine is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Dolutegravir: (Major) Avoid concurrent use of dolutegravir with oxcarbazepine, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Oxcarbazepine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Dolutegravir; Rilpivirine: (Severe) Concurrent use of oxcarbazepine and rilpivirine is contraindicated. When these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Oxcarbazepine is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine. (Major) Avoid concurrent use of dolutegravir with oxcarbazepine, as coadministration may result in decreased dolutegravir plasma concentrations. Currently, there are insufficient data to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Oxcarbazepine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Doravirine: (Severe) Concurrent administration of doravirine and oxcarbazepine is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; oxcarbazepine is a CYP3A4 inducer.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Severe) Concurrent administration of doravirine and oxcarbazepine is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; oxcarbazepine is a CYP3A4 inducer.
    Doxepin: (Moderate) Use doxepin with caution in patients with a history of seizures; doxepin may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of doxepin and oxcarbazepine may result in additive CNS depression. Oxcarbazepine, a CYP2C19 inhibitor, can increase plasma concentrations of doxepin, a substrate of CYP2C19.
    Doxorubicin: (Major) Oxcarbazepine is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of oxcarbazepine and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with oxcarbazepine is necessary, and monitor for a decrease in the efficacy of dronabinol. Additive dizziness, confusion, somnolence, and other CNS effects may also occur. Dronabinol is a CYP2C9 and 3A4 substrate; oxcarbazepine is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
    Dronedarone: (Major) The concomitant use of dronedarone and CYP3A4 inducers should be avoided. Dronedarone is metabolized by CYP3A. Oxcarbazepine induces CYP3A4. Coadministration of CYP3A4 inducers, such as oxcarbazepine, with dronedarone may result in reduced plasma concentration and subsequent reduced effectiveness of dronedarone therapy.
    Drospirenone; Estradiol: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Drospirenone; Ethinyl Estradiol: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Elvitegravir: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Oxcarbazepine induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with oxcarbazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Severe) Concurrent use of oxcarbazepine and rilpivirine is contraindicated. When these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Oxcarbazepine is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Severe) Concurrent use of oxcarbazepine and rilpivirine is contraindicated. When these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Oxcarbazepine is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Enalapril; Felodipine: (Moderate) The AUC of felodipine was decreased by 28% during repeated administration with oxcarbazepine. This interaction can be anticipated because felodipine is metabolized through the CYP3A4 isoenzyme which is induced by oxcarbazepine and its active metabolite, MHD.
    Enzalutamide: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if enzalutamide and oxcarbazepine are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of enzalutamide. Enzalutamide is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased plasma concentrations of MHD by 25% to 40%.
    Erlotinib: (Moderate) There may be a risk of reduced erlotinib efficacy when coadministered with oxcarbazepine; however, the risk has not been clearly defined. If coadministration is necessary, consider increasing the erlotinib dose by 50 mg increments at 2-week intervals as tolerated, to a maximum of 450 mg. Erlotinib is a CYP3A4 substrate, and oxcarbazepine is a moderate CYP3A4 inducer.
    Eslicarbazepine: (Severe) Eslicarbazepine is a prodrug for the active metabolite of oxcarbazepine and should therefore not be used as adjunctive therapy with oxcarbazepine.
    Esterified Estrogens: (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Esterified Estrogens; Methyltestosterone: (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Estradiol Cypionate; Medroxyprogesterone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Estradiol: (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Estradiol; Levonorgestrel: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Estradiol; Norethindrone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Estradiol; Norgestimate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Estrogens: (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Estropipate: (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethanol: (Moderate) Use of alcohol should be avoided in patients receiving oxcarbazepine. An additive CNS depressant effect can be expected during the concurrent use of ethanol and oxcarbazepine.
    Ethinyl Estradiol: (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Desogestrel: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Etonogestrel: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Levonorgestrel: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Norelgestromin: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Norethindrone Acetate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Norethindrone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Norgestimate: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ethinyl Estradiol; Norgestrel: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Etonogestrel: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Etoposide, VP-16: (Major) Monitor for clinical efficacy of etoposide if used concomitantly with oxcarbazepine. Oxcarbazepine is an inducer of CYP3A4; etoposide, VP-16 is a CYP3A4 substrate. Coadministration of etoposide with a strong CYP3A4 inducer (phenytoin) resulted in increased etoposide clearance and reduced efficacy, as did coadministration with a weak inducer of CYP3A4 and P-glycoprotein (P-gp) (valproic acid).
    Ezetimibe; Simvastatin: (Minor) Oxcarbazepine which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including simvastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are coadministered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Felodipine: (Moderate) The AUC of felodipine was decreased by 28% during repeated administration with oxcarbazepine. This interaction can be anticipated because felodipine is metabolized through the CYP3A4 isoenzyme which is induced by oxcarbazepine and its active metabolite, MHD.
    Flibanserin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as oxcarbazepine, is not recommended.
    Food: (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with oxcarbazepine. Oxcarbazepine is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with oxcarbazepine, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be increased. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Fosphenytoin: (Moderate) Monitor phenytoin concentrations during oxcarbazepine dosage titration or modification, and monitor plasma concentrations of MHD, the active metabolite of oxcarbazepine, during oxcarbazepine titration if oxcarbazepine and fosphenytoin are used concurrently. A dose adjustment of fosphenytoin or oxcarbazepine may be required. Phenytoin concentrations increased up to 40% with concomitant use of phenytoin (250 to 500 mg/day) and oxcarbazepine (1,200 to 2,400 mg/day). Coadministration of phenytoin (250 to 500 mg/day) with oxcarbazepine (600 to 2,400 mg/day) decreased MHD concentrations by 30%.
    Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Haloperidol: (Major) Significant reductions in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and CYP3A4 enzyme-inducing drugs such as carbamazepine. Oxcarbazepine is an inducer of CYP3A4. In addition, decreased anticonvulsant efficacy is a possibility when an antipsychotic agent such as haloperidol is administered to patients receiving oxcarbazepine for a seizure disorder, because antipsychotics may lower the seizure threshold. Haloperidol dosage adjustments should be made as needed when oxcarbazepine is added or discontinued.
    Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Hydrocodone; Ibuprofen: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of hydrocodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Hydroxyprogesterone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of oxycodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Imipramine: (Moderate) Use imipramine with caution in patients with a history of seizures; imipramine may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of imipramine and oxcarbazepine may result in additive CNS depression. Oxcarbazepine, a CYP2C19 inhibitor, can increase plasma concentrations of imipramine, a substrate of CYP2C19.
    Isavuconazonium: (Major) Caution and close monitoring are warranted when isavuconazonium is administered with oxcarbazepine as there is a potential for decreased concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; oxcarbazepine is an inducer of this enzyme.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if oxcarbazepine and rifampin are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of rifampin. Rifampin is a strong CYP3A4 inducer and a UGT inducer. Coadministration with other strong CYP3A4 inducers and/or UGT inducers decreased MHD concentrations by 25% to 40%.
    Isoniazid, INH; Rifampin: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if oxcarbazepine and rifampin are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of rifampin. Rifampin is a strong CYP3A4 inducer and a UGT inducer. Coadministration with other strong CYP3A4 inducers and/or UGT inducers decreased MHD concentrations by 25% to 40%.
    Ivabradine: (Major) Avoid coadministration of ivabradine and oxcarbazepine. Ivabradine is primarily metabolized by CYP3A4; oxcarbazepine is an inducer of CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
    Kava Kava, Piper methysticum: (Major) The German Commission E warns that any substances that act on the CNS, including anticonvulsants, may interact with kava kava. While the interactions can be pharmacodynamic in nature, kava kava has been reported to inhibit many CYP isozymes (i.e., CYP1A2, 2C9, 2C19, 2D6, 3A4, and 4A9/11) and important pharmacokinetic interactions with CNS-active agents that undergo oxidative metabolism via these CYP isozymes are also possible. Persons taking an anticonvulsant should discuss the use of herbal supplements with their health care professional prior to consuming them.
    Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., oxcarbazepine), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
    Ledipasvir; Sofosbuvir: (Major) Avoid coadministration of ledipasvir with oxcarbazepine. Taking these drugs together may decrease ledipasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of sofosbuvir with oxcarbazepine. Taking these drugs together may decrease sofosbuvir plasma concentration, potentially resulting in loss of antiviral efficacy.
    Leuprolide; Norethindrone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Levonorgestrel: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Lofexidine: (Moderate) Monitor for additive sedation during coadministration of lofexidine and anticonvulsants. Lofexidine can potentiate the effects of CNS depressants. Patients should be advised to avoid driving or performing any other tasks requiring mental alertness until the effects of the combination are known.
    Loperamide: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with oxcarbazepine. Loperamide is metabolized by the hepatic enzyme CYP3A4; oxcarbazepine is an inducer of this enzyme.
    Loperamide; Simethicone: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with oxcarbazepine. Loperamide is metabolized by the hepatic enzyme CYP3A4; oxcarbazepine is an inducer of this enzyme.
    Lopinavir; Ritonavir: (Major) Concurrent administration of oxcarbazepine with ritonavir should be undertaken with caution and careful monitoring of antiviral efficacy. Oxcarbazepine is a moderate inducer of the hepatic isoenzyme CYP3A4, and ritonavir is a CYP3A4 substrate.
    Lovastatin: (Minor) Oxcarbazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including lovastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Lovastatin; Niacin: (Minor) Oxcarbazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including lovastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Lumacaftor; Ivacaftor: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if oxcarbazepine and lumacaftor are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of lumacaftor. Lumacaftor is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased plasma concentrations of MHD by 25% to 40%.
    Lumacaftor; Ivacaftor: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if oxcarbazepine and lumacaftor are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of lumacaftor. Lumacaftor is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased plasma concentrations of MHD by 25% to 40%.
    Maraviroc: (Moderate) Use caution if coadministration of maraviroc with oxcarbazepine is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and oxcarbazepine is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
    Medroxyprogesterone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Mefloquine: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
    Mephobarbital: (Moderate) An interaction is possible when oxcarbazepine is coadministered with phenobarbital, the major metabolite of mephobarbital. The mean concentration of MHD, the active metabolite of oxcarbazepine, was decreased in one study, whereas the mean phenobarbital concentration was increased. This interaction likely involves the effects of phenobarbital as an inducer of the CYP3A4 isoenzyme and MHD as an inhibitor of CYP2C19.
    Mestranol; Norethindrone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. (Moderate) Estrogens are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine with estrogens, oral contraceptives, or non-oral combination contraceptives, progestins may increase the hormone's elimination. If used for contraception, an alternate or additional form of contraception should be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Mitotane: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if mitotane and oxcarbazepine are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of mitotane. Mitotane is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased concentrations of MHD by 25% to 40%.
    Molindone: (Moderate) Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.
    Monoamine oxidase inhibitors: (Severe) MAOIs should not be coadministered at the same time with oxcarbazepine, a dibenzazepine-related drug. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. At least 7 days should elapse between discontinuation of oxcarbazepine and initiation of an MAOI. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering oxcarbazepine. When starting MAOI therapy after discontinuing oxcarbazepine, it is advised to begin the MAOI at one-half the normal starting dosage for at least the first week of therapy. Carefully monitor the patient. Watch carefully for other effects besides effects on blood pressure, such as sedation, confusion, and increased CNS depression. If oxcarbazepine is used for the treatment of epilepsy, be aware that MAOI effects can include lowering of seizure threshold in some patients.
    Niacin; Simvastatin: (Minor) Oxcarbazepine which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including simvastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are coadministered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Nisoldipine: (Major) Avoid coadministration of nisoldipine with oxcarbazepine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and oxcarbazepine is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
    Norethindrone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Norgestrel: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Nortriptyline: (Moderate) Use nortriptyline with caution in patients with a history of seizures; nortriptyline may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of nortriptyline and oxcarbazepine may result in additive CNS depression.
    Ombitasvir; Paritaprevir; Ritonavir: (Severe) Concurrent administration of oxcarbazepine with dasabuvir; ombitasvir; paritaprevir; ritonavir is contraindicated. Taking these drugs together could result in decreased plasma concentrations of paritaprevir, ritonavir, and dasabuvir, which may affect antiviral efficacy. Oxcarbazepine is a moderate inducer of the hepatic isoenzyme CYP3A4, and ritonavir, paritaprevir, and dasabuvir (minor) are CYP3A4 substrates. (Major) Concurrent administration of oxcarbazepine with ritonavir should be undertaken with caution and careful monitoring of antiviral efficacy. Oxcarbazepine is a moderate inducer of the hepatic isoenzyme CYP3A4, and ritonavir is a CYP3A4 substrate.
    Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of oxycodone as needed. If oxcarbazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Pazopanib: (Moderate) Pazopanib is a substrate for CYP3A4. Plasma pazopanib concentrations may be decreased by concurrent administration with a CYP3A4 inducer such as oxcarbazepine. Use caution if chronic use of CYP3A4 inducers and pazopanib can not be avoided.
    Pemoline: (Major) A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents. Dosage adjustments of anticonvulsants may be necessary during simultaneous use of these drugs.
    Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with oxcarbazepine due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of oxcarbazepine occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Oxcarbazepine is a moderate CYP3A4 inducer, and perampanel is a CYP3A4 substrate. Oxcarbazepine reduced the AUC of perampanel by approximately 48% during concomitant use. Additionally, oxcarbazepine clearance decreased by 26%.
    Perindopril; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as oxcarbazepine, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
    Perphenazine; Amitriptyline: (Moderate) Use amitriptyline with caution in patients with a history of seizures; amitriptyline may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of amitriptyline and oxcarbazepine may result in additive CNS depression. Oxcarbazepine, a CYP2C19 inhibitor, can increase plasma concentrations of amitriptyline, a substrate of CYP2C19.
    Phenobarbital: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if phenobarbital and oxcarbazepine are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of phenobarbital. Additive CNS depression may also occur. Coadministration of oxcarbazepine (600 to 1,800 mg/day) with phenobarbital (100 to 150 mg/day) decreased the plasma concentration of MHD by 25% and increased the plasma concentration of phenobarbital by 14%. Strong CYP3A4 inducers and UGT inducers have been shown to decrease plasma concentrations of MHD. Phenobarbital is a strong CYP3A4 inducer and UGT inducer.
    Phenytoin: (Moderate) Monitor phenytoin concentrations during oxcarbazepine dosage titration or modification, and monitor plasma concentrations of MHD, the active metabolite of oxcarbazepine, during oxcarbazepine titration if oxcarbazepine and phenytoin are used concurrently. A dose adjustment of phenytoin or oxcarbazepine may be required. Phenytoin concentrations increased up to 40% with concomitant use of phenytoin (250 to 500 mg/day) and oxcarbazepine (1,200 to 2,400 mg/day). Coadministration of phenytoin (250 to 500 mg/day) with oxcarbazepine (600 to 2,400 mg/day) decreased MHD concentrations by 30%.
    Praziquantel: (Major) In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Therefore, use of praziquantel with oxcarbazepine, a CYP3A4 inducer, should be done with caution as concomitant use may produce therapeutically ineffective concentrations of praziquantel.
    Primidone: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if primidone and oxcarbazepine are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of primidone. Additive CNS depression may also occur. Coadministration of oxcarbazepine (600 to 1,800 mg/day) with phenobarbital (100 to 150 mg/day), the active metabolite of primidone, decreased the plasma concentration of MHD by 25% and increased the plasma concentration of phenobarbital by 14%. Strong CYP3A4 inducers and UGT inducers have been shown to decrease plasma concentrations of MHD. Primidone is a strong CYP3A4 inducer, and phenobarbital is a strong CYP3A4 inducer and UGT inducer.
    Progesterone: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Progestins: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy.
    Protriptyline: (Moderate) Use protriptyline with caution in patients with a history of seizures; protriptyline may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of protriptyline and oxcarbazepine may result in additive CNS depression.
    Red Yeast Rice: (Moderate) Since certain red yeast rice products (i.e., pre-2005 Cholestin formulations) contain lovastatin, clinicians should use red yeast rice cautiously in combination with drugs known to interact with lovastatin. CYP3A4 inducers can theoretically reduce the effectiveness of HMG-CoA reductase activity via induction of CYP3A4 metabolism. Examples of CYP3A4 inducers include oxcarbazepine.
    Rifampin: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if oxcarbazepine and rifampin are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of rifampin. Rifampin is a strong CYP3A4 inducer and a UGT inducer. Coadministration with other strong CYP3A4 inducers and/or UGT inducers decreased MHD concentrations by 25% to 40%.
    Rilpivirine: (Severe) Concurrent use of oxcarbazepine and rilpivirine is contraindicated. When these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Oxcarbazepine is a potent inducer of CYP3A4, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
    Ritonavir: (Major) Concurrent administration of oxcarbazepine with ritonavir should be undertaken with caution and careful monitoring of antiviral efficacy. Oxcarbazepine is a moderate inducer of the hepatic isoenzyme CYP3A4, and ritonavir is a CYP3A4 substrate.
    Simeprevir: (Major) Avoid concurrent use of simeprevir and oxcarbazepine. Induction of CYP3A4 by oxcarbazepine may significantly reduce the plasma concentrations of simeprevir, resulting in treatment failure.
    Simvastatin: (Minor) Oxcarbazepine which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including simvastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are coadministered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Simvastatin; Sitagliptin: (Minor) Oxcarbazepine which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates including simvastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are coadministered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
    Sofosbuvir: (Major) Avoid coadministration of sofosbuvir with oxcarbazepine. Taking these drugs together may decrease sofosbuvir plasma concentration, potentially resulting in loss of antiviral efficacy.
    Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of sofosbuvir with oxcarbazepine. Taking these drugs together may decrease sofosbuvir plasma concentration, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of CYP3A4, such as oxcarbazepine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of sofosbuvir with oxcarbazepine. Taking these drugs together may decrease sofosbuvir plasma concentration, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of CYP3A4, such as oxcarbazepine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate. (Major) Avoid coadministration of voxilaprevir with moderate to potent inducers of CYP3A4, such as oxcarbazepine. Taking these drugs together may significantly decrease voxilaprevir plasma concentrations, potentially resulting in loss of antiviral efficacy. Voxilaprevir is metabolized by CYP3A4.
    St. John's Wort, Hypericum perforatum: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if St. John's Wort and oxcarbazepine are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of St. John's Wort. St. John's Wort is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased plasma concentrations of MHD by 25% to 40%.
    Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if oxcarbazepine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with oxcarbazepine is necessary; consider increasing the dose of sufentanil injection as needed. If oxcarbazepine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Sunitinib: (Major) Avoid coadministration of oxcarbazepine with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the dose of sunitinib in 12.5 mg increments based on individual safety and tolerability to a maximum of 87.5 mg (GIST and RCC) or 62.5 mg (pNET) daily; monitor carefully for toxicity. The maximum daily dose administered in the pNET study was 50 mg. Sunitinib is a CYP3A4 substrate and oxcarbazepine is a moderate CYP3A4 inducer.
    Tacrolimus: (Moderate) The effectiveness of immunosuppressive medications such as tacrolimus could be decreased by the co-administration of oxcarbazepine. Monitoring of tacrolimus whole blood concentrations is recommended if oxcarbazepine is used concurrently with tacrolimus.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering oxcarbazepine with telaprevir due to the potential for telaprevir treatment failure. If oxcarbazepine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of oxcarbazepine and telaprevir. Oxcarbazepine is an inducer of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may decrease, resulting in decreased telaprevir efficacy.
    Telithromycin: (Major) Oxcarbazepine and its active metabolite, MHD, are dose-dependent inducers of the hepatic CYP3A4 isoenzyme thereby having the potential to lower the plasma levels of medications metabolized through these pathways, such a telithromycin.
    Tenofovir Alafenamide: (Major) Administering tenofovir alafenamide with oxcarbazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
    Tolvaptan: (Major) Tolvaptan is metabolized by CYP3A4. Oxcarbazepine is an inducer of CYP3A4. Coadministration may result in reduced plasma concentration and subsequent reduced effectiveness of tolvaptan therapy and should be avoided. If coadministration is unavoidable, an increase in the tolvaptan dose may be necessary and patients should be monitored for decreased effectiveness of tolvaptan.
    Trandolapril; Verapamil: (Minor) Verapamil may decrease the plasma levels of MHD, the active metabolite of oxcarbazepine. The mechanism is not clear since it is contrary to the typical interactions seen with verapamil which are the result of its hepatic CYP3A4 inhibition.
    Trimipramine: (Moderate) Use trimipramine with caution in patients with a history of seizures; trimipramine may lower the seizure threshold and thus potentially interfere with the ability of antiepileptics to control seizures. In addition, concomitant use of trimipramine and oxcarbazepine may result in additive CNS depression.
    Ulipristal: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and oxcarbazepine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
    Verapamil: (Minor) Verapamil may decrease the plasma levels of MHD, the active metabolite of oxcarbazepine. The mechanism is not clear since it is contrary to the typical interactions seen with verapamil which are the result of its hepatic CYP3A4 inhibition.
    Vinblastine: (Minor) Use caution when administering vinblastine concurrently with a CYP3A4 inducer such as oxcarbazepine. Vinblastine is metabolized by CYP3A4 and oxcarbazepine may decrease vinblastine plasma concentrations.
    Vincristine Liposomal: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, include oxcarbazepine. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
    Vincristine: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, include oxcarbazepine. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate data on the developmental risk associated with oxcarbazepine use during human pregnancy. Data from pregnancy registries suggest that oxcarbazepine monotherapy is associated with craniofacial defects such as oral clefts and cardiac malformations such as ventricular septal defects. An increase in seizure frequency may occur during pregnancy due to altered concentrations of the active metabolite of oxcarbazepine. Monitor patients carefully during pregnancy and the postpartum period. Oxcarbazepine is structurally related to carbamazepine, which is considered to be teratogenic in humans. Increased incidences of fetal structural abnormalities, embryolethality, and growth retardation were observed in offspring of animals treated with oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at exposures similar to the maximum recommended human dose. Encourage women taking oxcarbazepine during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.[29014]

    Oxcarbazepine and its active metabolite (MHD) are excreted in human breast milk. The effects of oxcarbazepine and its active metabolite on the breast-fed infant or on milk production are unknown.[29014] Milk to plasma ratios of 0.5 and 0.5 to 0.8 for oxcarbazepine and MHD, respectively, have been reported. Based on concentrations of oxcarbazepine in the breast milk of 1 mother taking 600 mg/day (weight-corrected dose of 9 mg/kg), it was estimated that an exclusively breast-fed infant with an average milk ingestion of 0.15 L/kg per day would receive approximately 1.5% to 1.7% of the maternal weight-adjusted dose. Infant plasma concentrations of oxcarbazepine and its metabolite on days 8 and 23 postpartum were less than 0.1 to 0.2 mcg/mL. The infant was breast fed for a total of 18 weeks; no adverse events or developmental delays were observed up to 5 years of age.[46392] Previous American Academy of Pediatrics (AAP) recommendations considered carbamazepine to be usually compatible with breast-feeding; however, the AAP did not evaluate oxcarbazepine.[27500] Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for oxcarbazepine and any potential adverse effects on the breast-fed infant from oxcarbazepine or the underlying maternal condition.[29014]

    MECHANISM OF ACTION

    Mechanism of Action: The primary pharmacologic activity is attributed to the 10-monohydroxy metabolite (MHD) of oxcarbazepine because of the rapid systemic metabolism of the parent compound. Like most anticonvulsants, the exact mechanism of action is unknown; however, in vitro studies indicate that voltage-sensitive sodium channels are blocked thereby stabilizing neural membranes, inhibiting repetitive neuronal firing, and diminishing synaptic impulse activity. Modulation of potassium and calcium channels may also be involved. GABA receptors are not affected by oxcarbazepine or MHD.

    PHARMACOKINETICS

    Oxcarbazepine is administered orally. Following absorption, it undergoes rapid reduction in the liver to MHD. Peak MHD plasma levels are reached in 4—6 hours while steady state levels are attained within 2—3 days of twice daily dosing. The half-lives of oxcarbazepine and MHD are 2 and 9 hours, respectively. MHD is metabolized primarily through conjugation to minor metabolites. About 4% of MHD is oxidized through hepatic CYP3A4/5 isoenzymes. More than 95% of the dose is renally excreted; however, less than 1% is unchanged oxcarbazepine. Almost one-half of a dose is eliminated as metabolites of MHD. Less than 4% of a dose is excreted in the feces.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2C19, CYP3A4/5
    Oxcarbazepine (and MHD) are dose-dependent inhibitors of CYP2C19. During use of high doses of oxcarbazepine with a CYP2C19 substrate, such as phenytoin, a significant interaction can occur. Similar to carbamazepine, oxcarbazepine and MHD can cause clinically relevant interactions through induction of CYP3A4; however, oxcarbazepine is a less potent inducer of CYP3A4 than carbamazepine.

    Oral Route

    Following oral administration, oxcarbazepine is almost completely absorbed from the gastrointestinal tract. Food does not affect the rate or extent of absorption.