Trileptal

Carboxamide Anticonvulsants

Hazardous Drugs Classification
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.

visual impairment / Early / 4.0-14.0
hyponatremia / Delayed / 1.2-2.5
seizures / Delayed / Incidence not known
muscle paralysis / Delayed / Incidence not known
suicidal ideation / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
hematemesis / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
erythema multiforme / 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
SIADH / Delayed / Incidence not known
water intoxication / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
bone fractures / Delayed / Incidence not known
ocular hemorrhage / Delayed / Incidence not known
bradycardia / Rapid / Incidence not known
heart failure / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known

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
EEG changes / Delayed / 0-2.0
nystagmus / Delayed / 2.0-2.0
dysarthria / Delayed / 2.0-2.0
hot flashes / Early / 2.0-2.0
peripheral edema / Delayed / 1.0-2.0
chest pain (unspecified) / Early / 2.0-2.0
edema / Delayed / 2.0-2.0
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
hypotonia / Delayed / Incidence not known
hyperreflexia / Delayed / Incidence not known
migraine / Early / Incidence not known
impaired cognition / Early / Incidence not known
psychosis / Early / Incidence not known
mania / Early / Incidence not known
depression / Delayed / Incidence not known
delirium / Early / Incidence not known
euphoria / Early / Incidence not known
stomatitis / Delayed / Incidence not known
cholelithiasis / Delayed / Incidence not known
hemorrhoids / Delayed / Incidence not known
colitis / Delayed / Incidence not known
gingival hyperplasia / Delayed / Incidence not known
melena / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
psoriasis / Delayed / Incidence not known
atopic dermatitis / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
dyspnea / Early / Incidence not known
osteoporosis / Delayed / Incidence not known
hypertonia / Delayed / Incidence not known
ocular inflammation / Early / Incidence not known
photophobia / Early / Incidence not known
cataracts / Delayed / Incidence not known
scotomata / Delayed / Incidence not known
hypertension / Early / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
palpitations / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hematuria / Delayed / Incidence not known
dysuria / Early / Incidence not known
priapism / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / 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

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
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
insomnia / Early / 6.0-6.0
tremor / Early / 4.0-6.0
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
acne vulgaris / Delayed / 1.0-2.0
purpura / Delayed / 2.0-2.0
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
gingivitis / Delayed / Incidence not known
weight loss / Delayed / Incidence not known
appetite stimulation / Delayed / Incidence not known
flatulence / Early / Incidence not known
eructation / Early / Incidence not known
hiccups / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
flushing / Rapid / Incidence not known
folliculitis / Delayed / Incidence not known
malaise / Early / Incidence not known
infection / Delayed / Incidence not known
vertigo / Early / Incidence not known
mydriasis / Early / Incidence not known
tinnitus / Delayed / Incidence not known
xerophthalmia / Early / Incidence not known
syncope / Early / Incidence not known
menorrhagia / Delayed / Incidence not known
leukorrhea / Delayed / Incidence not known
menstrual irregularity / Delayed / Incidence not known
polyuria / Early / Incidence not known
polydipsia / Early / Incidence not known

Oxtellar XR, Trileptal

Rx

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

†Indicates off-label use

Oxcarbazepine use is not recommended in patients with severe hepatic impairment; the pharmacokinetics of oxcarbazepine and MHD have not been evaluated in these patients.

Immediate-release tablets or oral solution
CrCl 30 mL/minute or more: No dosage adjustment needed.
CrCl less than 30 mL/minute: Start at one-half the usual starting dose and increase slowly to achieve desired clinical response.
 
Extended-release tablets (Adults)
CrCl 30 mL/minute or more: No dosage adjustment needed.
CrCl less than 30 mL/minute: Start at one-half the usual starting dose (i.e., 300 mg/day). Subsequent dosage increases can be made at weekly intervals in increments of 300 to 450 mg/day to achieve the desired clinical response.
 
Hemodialysis
In patients with end-stage renal disease on dialysis, it is recommended that an immediate-release oxcarbazepine formulation be used instead of extended-release tablets.

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.
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.
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; Celecoxib: (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; 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; Valsartan; 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.
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; 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.
Atogepant: (Major) Avoid use of atogepant and oxcarbazepine when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with oxcarbazepine. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and oxcarbazepine is a weak CYP3A inducer. Coadministration with a weak CYP3A inducer resulted in a 25% reduction in atogepant overall exposure and a 24% reduction in atogepant peak concentration.
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.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of oxcarbazepine with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and oxcarbazepine is a CYP2C19 inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with oxcarbazepine may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of oxcarbazepine may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If oxcarbazepine is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Oxcarbazepine is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Consider an alternative anticonvulsant during treatment with bictegravir. Concomitant use of bictegravir and oxcarbazepine may result in decreased bictegravir plasma concentrations, which may result in the loss of therapeutic efficacy and development of resistance.
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.
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; Naltrexone: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold.
Cabotegravir: (Contraindicated) Coadministration of cabotegravir and oxcarbazepine is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; oxcarbazepine is an inducer of UGT. Coadministration with another UGT inducer decreased cabotegravir exposure by 59%.
Cabotegravir; Rilpivirine: (Contraindicated) Coadministration of cabotegravir and oxcarbazepine is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; oxcarbazepine is an inducer of UGT. Coadministration with another UGT inducer decreased cabotegravir exposure by 59%. (Contraindicated) 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.
Canagliflozin: (Major) Increase the canagliflozin dose to 200 mg/day in persons who are tolerating canagliflozin 100 mg/day and receiving concomitant oxcarbazepine. The canagliflozin dose may be further increased to 300 mg/day for persons with an eGFR of 60 mL/minute/1.73 m2 or more who require additional glycemic control; consider adding another antihyperglycemic agent for persons with an eGFR less than 60 mL/minute/1.73 m2 who require additional glycemic control. Canagliflozin is an UGT1A9 and UGT2B4 substrate, and oxcarbazepine is an UGT inducer. Coadministration with a nonselective inducer of several UGT enzymes decreased canagliflozin exposure by 51%. This decrease in exposure may decrease canagliflozin efficacy.
Canagliflozin; Metformin: (Major) Increase the canagliflozin dose to 200 mg/day in persons who are tolerating canagliflozin 100 mg/day and receiving concomitant oxcarbazepine. The canagliflozin dose may be further increased to 300 mg/day for persons with an eGFR of 60 mL/minute/1.73 m2 or more who require additional glycemic control; consider adding another antihyperglycemic agent for persons with an eGFR less than 60 mL/minute/1.73 m2 who require additional glycemic control. Canagliflozin is an UGT1A9 and UGT2B4 substrate, and oxcarbazepine is an UGT inducer. Coadministration with a nonselective inducer of several UGT enzymes decreased canagliflozin exposure by 51%. This decrease in exposure may decrease canagliflozin efficacy.
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.
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.
Chlordiazepoxide; 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.
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; 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.
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.
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; 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.
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.
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.
Desogestrel; 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.
Dextromethorphan; Bupropion: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold.
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.
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; 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.
Dolutegravir; Rilpivirine: (Contraindicated) 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: (Contraindicated) 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: (Contraindicated) 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 Liposomal: (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.
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.
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: (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.
Drospirenone; Estetrol: (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.
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.
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.
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.
Elagolix; 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.
Elvitegravir; Cobicistat; 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.
Elvitegravir; Cobicistat; 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.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) 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: (Contraindicated) 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.
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%.
Eslicarbazepine: (Contraindicated) Eslicarbazepine is a prodrug for the active metabolite of oxcarbazepine and should therefore not be used as adjunctive therapy with oxcarbazepine.
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.
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.
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.
Estradiol; 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.
Estrogens affected by CYP3A inducers: (Major) Women taking both estrogens and oxcarbazepine should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed oxcarbazepine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of oxcarbazepine. 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 are CYP3A4 substrates and oxcarbazepine is a CYP3A4 inducer. Concurrent administration has been shown to decrease the exposure of some estrogens by approximately 50%.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
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.
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.
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.
Ethynodiol Diacetate; 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.
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.
Etonogestrel; 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.
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.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of oxcarbazepine is necessary. If oxcarbazepine is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like oxcarbazepine with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
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.
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.
Haloperidol: (Moderate) Careful monitoring of clinical status is warranted when oxcarbazepine, an enzyme-inducing drug, is administered or discontinued in haloperidol-treated patients. Adjust the haloperidol dose as clinically necessary. After discontinuation of oxcarbazepine, it may be necessary to reduce the haloperidol dosage. Significant reductions in haloperidol plasma concentrations have been reported during concurrent use of CYP3A4 enzyme-inducing drugs. Because antipsychotics such as haloperidol may lower the seizure threshold, a reduction in anticonvulsant efficacy may also occur if oxcarbazepine is used for seizures. Additive CNS effects, such as sedation, may also occur in some patients.
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; 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.
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%.
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.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as oxcarbazepine. Concomitant use of oxcarbazepine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lansoprazole; Amoxicillin; 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.
Ledipasvir; Sofosbuvir: (Major) Avoid coadministration of sofosbuvir with oxcarbazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Lenacapavir: (Major) Avoid concurrent use of lenacapavir and oxcarbazepine due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance.
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.
Levamlodipine: (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.
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.
Levonorgestrel; 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.
Levonorgestrel; Ethinyl Estradiol; 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.
Levonorgestrel; Ethinyl Estradiol; 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.
Lopinavir; Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with oxcarbazepine. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and oxcarbazepine is a weak CYP3A inducer.
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.
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%.
Lumateperone: (Major) Avoid coadministration of lumateperone and oxcarbazepine as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; oxcarbazepine is a weak CYP3A4 inducer.
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.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting oxcarbazepine therapy. Avoid initiation of oxcarbazepine in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable oxcarbazepine therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and oxcarbazepine is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
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) Oxcarbazepine induces CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and anticonvulsants may also result in lower than expected oxcarbazepine anticonvulsant concentrations and loss of seizure control. Monitoring of the oxcarbazepine serum concentration is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Mitapivat: (Moderate) Monitor for decreased plasma levels of MHD, the active metabolite of oxcarbazepine, if coadministered with mitapivat. The oxcarbazepine dose may require adjustment after initiation, dosage modification, or discontinuation of mitapivat. UGT inducers like mitapivat have been shown to decrease MHD exposure by 25 to 49%.
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: (Contraindicated) 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.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with oxcarbazepine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with oxcarbazepine. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and oxcarbazepine is a weak CYP3A inducer.
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.
Nirmatrelvir; Ritonavir: (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of oxcarbazepine is necessary. Concomitant use of nirmatrelvir and oxcarbazepine may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and oxcarbazepine is a weak CYP3A inducer. (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with oxcarbazepine. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and oxcarbazepine is a weak CYP3A inducer.
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 Acetate; Ethinyl Estradiol; 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.
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.
Norethindrone; 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.
Norethindrone; Ethinyl Estradiol; 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.
Norgestimate; 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.
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.
Olmesartan; 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.
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.
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. Perampanel is a CYP3A substrate and oxcarbazepine is a CYP3A inducer. Oxcarbazepine has been observed to reduce the AUC of perampanel by approximately 48%.
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.
Phenobarbital; Hyoscyamine; Atropine; 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.
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.
Relugolix; 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.
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%.
Rifapentine: (Moderate) Monitor for decreased plasma levels of MHD, the active metabolite of oxcarbazepine, if coadministered with rifapentine. The oxcarbazepine dose may require adjustment after initiation, dosage modification, or discontinuation of rifapentine. Strong CYP3A4 inducers like rifapentine have been shown to decrease MHD exposure by 25 to 49%.
Rilpivirine: (Contraindicated) 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: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with oxcarbazepine. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and oxcarbazepine is a weak CYP3A inducer.
Segesterone Acetate; 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.
Selegiline: (Contraindicated) Oxcarbazepine is the keto-analogue of carbamazepine, which is contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with oxcarbazepine. After stopping treatment with oxcarbazepine, a time period equal to 4 to 5 half-lives of oxcarbazepine or any active metabolite should elapse before starting therapy with selegiline.
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.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of oxcarbazepine. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and oxcarbazepine is a weak CYP3A inducer.
Sofosbuvir: (Major) Avoid coadministration of sofosbuvir with oxcarbazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of sofosbuvir with oxcarbazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of sofosbuvir with oxcarbazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (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.
Sotagliflozin: (Moderate) Monitor for a decrease in sotagliflozin efficacy during concomitant use of sotagliflozin and oxcarbazepine and adjust therapy as appropriate. Concomitant use may decrease sotagliflozin exposure. Sotagliflozin is a UGT substrate and oxcarbazepine is a UGT inducer. Concomitant use with another UGT inducer reduced sotagliflozin overall exposure by 45%.
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.
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.
Telmisartan; 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.
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.
Trandolapril; Verapamil: (Moderate) Monitor for decreased plasma levels of MHD, the active metabolite of oxcarbazepine, if coadministered with verapamil. The oxcarbazepine dose may require adjustment after initiation, dosage modification, or discontinuation of verapamil. Verapamil has been shown to decrease MHD exposure by approximately 20%. The mechanism of interaction is unknown.
Trimipramine: (Moderate) Use trimipramine with caution in patients with a history of seizures; trimipramine may lower the seizure threshold and thus potentially interfere with th e ability of antiepileptics to control seizures. In addition, concomitant use of trimipramine and oxcarbazepine may result in additive CNS depression.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with oxcarbazepine as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; oxcarbazepine is a weak CYP3A4 inducer.
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: (Moderate) Monitor for decreased plasma levels of MHD, the active metabolite of oxcarbazepine, if coadministered with verapamil. The oxcarbazepine dose may require adjustment after initiation, dosage modification, or discontinuation of verapamil. Verapamil has been shown to decrease MHD exposure by approximately 20%. The mechanism of interaction is unknown.
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.
Vonoprazan; Amoxicillin; 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.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with oxcarbazepine is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Oxcarbazepine is a weak CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.

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

2,400 mg/day PO.

2,400 mg/day PO.

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.

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.

Safety and efficacy have not been established.

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.

Oxcarbazepine is administered orally. After absorption, it undergoes rapid reduction in the liver to its pharmacologically active 10-monohydroxy metabolite (MHD). The apparent Vd of MHD is 49 L. Approximately 40% of MHD is bound to serum proteins, predominantly to albumin. 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. After administration of immediate-release oxcarbazepine, the half-life of oxcarbazepine is about 2 hours, and the half-life of MHD is about 9 hours. In clinical studies of extended-release oxcarbazepine, the half-life of oxcarbazepie was 7 to 11 hours, and the half-life of MHD was 9 to 11 hours.
 
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.

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. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to oxcarbazepine; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.[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]