PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Carboxamide Anticonvulsants
    Mood Stabilizers
    Neuropathic Pain and Peripheral Neuropathy Agents

    BOXED WARNING

    Asian patients, serious rash

    Carbamazepine may cause life-threatening serious rash, including Stevens-Johnson syndrome and toxic epidermal necrolysis. The estimated risk of developing these serious adverse effects is about 1 to 6 per 10,000 new users of carbamazepine in countries of mainly Caucasian populations, and an estimated risk which is 10 times higher in some Asian countries. The inherited variant of an immune system gene (HLA-B 1502), which is associated with the development of some serious skin reactions, is most prevalent in Asians. Therefore, it is recommended that Asian patients undergo a genetic blood test prior to initiation of carbamazepine treatment. The benefits of treatment with carbamazepine should be weighed against the risks in patients who test positive for HLA-B 1502. The test does not appear to be beneficial in those who have been taking carbamazepine for more than a few months, since it is unlikely that the skin reactions will develop after that time regardless of the presence or absence of the variant gene.

    Agranulocytosis, aplastic anemia, bone marrow suppression, hematological disease, leukopenia, neutropenia, thrombocytopenia

    Carbamazepine is contraindicated in patients with a history of bone marrow suppression. Carbamazepine should be used with caution in patients with blood dyscrasias caused by drug therapies or hematological disease because of the potential increased risk of hematologic toxicity. Although uncommon, carbamazepine can cause hematological toxicity consisting of transient leukopenia, neutropenia, thrombocytopenia, or more severe reactions like agranulocytosis or aplastic anemia. Case-control population data have demonstrated that the risk of developing these reactions is 5—8 times greater in patients treated with carbamazepine than in the general population. However aplastic anemia and agranulocytosis are rare in the untreated general population (i.e., 1—2 persons per one million population per year). It would be uncommon for a patient who is taking carbamazepine to develop a severe blood dyscrasia, even if hematologic changes occur during treatment. Pretreatment baseline hematologic counts should be obtained. Periodic hematologic testing during treatment is recommended; if a patient develops neutropenia or thrombocytopenia the patient should be closely monitored. Discontinuation of carbamazepine should be considered if significant bone marrow suppression develops.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral antiepileptic, specific analgesic, and mood stabilizer
    Used for partial and tonic-clonic seizures, trigeminal neuralgia, and bipolar I disorder
    Monitor for emerging or worsening depression, suicidal thoughts/behavior, or mood/behavior changes

    COMMON BRAND NAMES

    Carbatrol, Epitol, Equetro, Tegretol, Tegretol -XR

    HOW SUPPLIED

    Carbamazepine/Carbatrol/Equetro Oral Cap ER: 100mg, 200mg, 300mg
    Carbamazepine/Epitol/Tegretol Oral Tab: 200mg
    Carbamazepine/Tegretol Oral Susp: 5mL, 100mg
    Carbamazepine/Tegretol Oral Tab Chew: 100mg
    Carbamazepine/Tegretol -XR Oral Tab ER: 100mg, 200mg, 400mg

    DOSAGE & INDICATIONS

    For the management of generalized tonic-clonic seizures, or for partial seizures, either simple or complex-partial seizures.
    NOTE: Periodic monitoring of serum carbamazepine concentrations is recommended.
    Oral dosage (regular-release tablets)
    Adults

    Initially, 200 mg PO twice daily. Increase in weekly increments of 200 mg/day, as needed, up to 1600 mg PO per day given in 3 or 4 divided doses.

    Adolescents 16 years and older

    Initially, 200 mg PO twice daily. Increase in weekly increments of 200 mg/day, as needed, up to 1200 mg PO per day given in 3 or 4 divided doses.

    Children and Adolescents 12 to 15 years

    Initially, 200 mg PO twice daily. Increase in weekly increments of 200 mg/day, as needed, up to 1000 mg PO per day given in 3 or 4 divided doses.

    Children 6 to 11 years

    Initially, 100 mg PO twice daily. Increase in weekly increments of 100 mg/day, as needed, up to 1000 mg PO per day given in 3 or 4 divided doses.

    Children younger than 6 years

    Initially, 10 to 20 mg/kg/day PO given in 2 or 3 divided doses. Increase weekly, as needed, up to 35 mg/kg/day given in 3 or 4 divided doses. The safety of doses above 35 mg/kg/day has not been established.

    Oral dosage (suspension)
    Adults

    Initially, 100 mg PO 4 times daily. Increase in weekly increments of 200 mg/day, as needed, up to 1600 mg PO per day given in 3 or 4 divided doses.

    Adolescents 16 years and older

    Initially, 100 mg PO 4 times daily. Increase in weekly increments of 200 mg/day, as needed, up to 1200 mg PO per day given in 3 or 4 divided doses.

    Children and Adolescents 12 to 15 years

    Initially, 100 mg PO 4 times daily. Increase in weekly increments of 200 mg/day, as needed, up to 1000 mg PO per day given in 3 or 4 divided doses.

    Children 6 to 11 years

    Initially, 50 mg PO 4 times daily. Increase in weekly increments of 100 mg/day, as needed, up to 1000 mg PO per day given in 3 or 4 divided doses.

    Children younger than 6 years

    Initially, 10 to 20 mg/kg/day PO given in 4 divided doses. Increase weekly, as needed, up to 35 mg/kg/day given in 3 or 4 divided doses. The safety of doses above 35 mg/kg/day has not been established.

    Oral dosage (extended-release tablets)
    Adults

    Initially, 200 mg PO twice daily. Increase in weekly increments of 200 mg/day every 12 hours, as needed, up to 1600 mg PO per day given in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.

    Adolescents 16 years and older

    Initially, 200 mg PO twice daily. Increase in weekly increments of 200 mg/day every 12 hours, as needed, up to 1200 mg PO per day given in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.

    Children and Adolescents 12 to 15 years

    Initially, 200 mg PO twice daily. Increase in weekly increments of 200 mg/day every 12 hours, as needed, up to 1000 mg PO per day given in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.

    Children 6 to 11 years

    Initially, 100 mg PO twice daily. Increase in weekly increments of 100 mg/day every 12 hours, as needed, up to 1000 mg PO per day given in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.

    Oral dosage (extended-release capsules)
    Adults

    Initially, 200 mg PO twice daily. Increase in weekly increments of 200 mg/day every 12 hours, as needed, up to 1600 mg PO per day given in 2 divided doses. To discontinue, gradually reduce the dose. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.

    Adolescents 16 years and older

    Initially, 200 mg PO twice daily. Increase in weekly increments of 200 mg/day every 12 hours, as needed, up to 1200 mg PO per day given in 2 divided doses. To discontinue, gradually reduce the dose. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.

    Children and Adolescents 12 to 15 years

    Initially, 200 mg PO twice daily. Increase in weekly increments of 200 mg/day every 12 hours, as needed, up to 1000 mg PO per day given in 2 divided doses. To discontinue, gradually reduce the dose. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.

    Children younger than 12 years

    Children taking immediate-release carbamazepine 400 mg/day PO or more can be converted to the same total daily dosage of the extended-release capsules using a twice-daily regimen. Optimal response is usually achieved at total doses less than 35 mg/kg/day. The safety of doses above 35 mg/kg/day has not been established. To discontinue, gradually reduce the dose.

    Intravenous dosage

    Intravenous carbamazepine should only be used as replacement therapy for oral formulations when oral administration is temporarily not feasible.

    Adults

    The total daily dose of IV carbamazepine is 70% of the total daily PO carbamazepine dose. Divide the total daily IV dose to be given every 6 hours. Resume therapy with oral carbamazepine as soon as clinically appropriate. The use of IV carbamazepine for more than 7 days has not been studied.

    For the symptomatic treatment of neuropathic pain.
    Associated with diabetic neuropathy†.
    Oral dosage (regular-release tablets)
    Adults

    Initially, 100 mg PO twice daily. Titrate dose to 600 to 800 mg/day or until side effects are intolerable.

    Oral dosage (suspension)
    Adults

    Initially, 50 mg PO 4 times daily. Titrate dose to 600 to 800 mg/day or until side effects are intolerable.

    Associated with postherpetic neuralgia†.
    Oral dosage (regular-release tablets or suspension)
    Adults

    100 to 300 mg PO 3 times daily. In a study of 77 patients, carbamazepine was added when patients complained of shooting pains unresponsive to amitriptyline and fluphenazine.

    Associated with trigeminal neuralgia.
    Oral dosage (regular-release or extended-release tablets)
    Adults

    Initially, 100 mg PO twice daily. Increase by up to 200 mg/day every 12 hours, as needed, up to 1200 mg PO per day given in 2 divided doses. Adequate control achieved in most patients with 400 to 800 mg/day PO given in 2 divided doses. Dose reduction or drug withdrawal should be attempted at least once every 3 months.

    Oral dosage (suspension)
    Adults

    Initially, 50 mg PO 4 times daily. Increase by up to 200 mg/day, as needed, up to 1200 mg PO per day given in 4 divided doses. Adequate control achieved in most patients with 400 to 800 mg/day PO given in 4 divided doses. Dose reduction or drug withdrawal should be attempted at least once every 3 months.

    Oral dosage (extended-release capsules)
    Adults

    Initially, 200 mg PO once daily. Increase by up to 200 mg/day every 12 hours, as needed, up to 1200 mg PO per day in 2 divided doses. Adequate control achieved in most patients with 400 to 800 mg/day PO given in 2 divided doses. Dose reduction or drug withdrawal should be attempted at least once every 3 months. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.

    For the treatment of acute mania and mixed episodes associated with bipolar disorder (bipolar I disorder).
    Oral dosage (immediate-release products)
    Adults

    Initially, 200 mg PO twice daily. Increase every 3 to 4 days to achieve a serum carbamazepine concentration of 8 to 12 mcg/mL. Usual daily dose range is 600 to 1600 mg/day PO in divided doses. Used as monotherapy or as adjunct therapy with lithium.

    Adolescents†

    Large, well-controlled, clinical trials of carbamazepine for pediatric bipolar disorder are lacking. In adolescents, doses of 200 mg PO twice daily have been used. Increase dose every 3 to 4 days to achieve a serum carbamazepine concentration of 8 to 12 mcg/mL. Usual daily dose range is 600 to 1600 mg/day PO in divided doses. In a 6-week open label study in children and adolescents aged 8 to 18 years, the initial dose was 15 mg/kg/day PO in 3 divided doses. Serum concentrations were measured after 1 week, and the dose was titrated until serum concentration was 7 to 10 mcg/mL. Clinical pediatric guideline algorithms include a recommendation of carbamazepine as one choice for first line monotherapy (Stage 1) treatment of nonpsychotic bipolar disorder I (manic or mixed) in pediatric patients 6 to 17 years of age. Other first line agents include: valproate, lithium, olanzapine, quetiapine, and risperidone. Both the clinical experience of the provider and the side effect profile of the medication for a given child must guide initial monotherapy selection. The panel recommended a minimum of 4 to 6 weeks at therapeutic blood levels and/or adequate dose for carbamazepine to assess initial response. In children with psychosis, combination therapy with a mood stabilizer, such as carbamazepine, and an atypical antipsychotic is suggested. Additional recommendations based on response to initial monotherapy and augmentation strategies can be found within the guideline and accompanying algorithms.

    Children† 6 to 12 years

    Large, well-controlled, clinical trials of carbamazepine for pediatric bipolar disorder are lacking. In a 6-week open label study in children and adolescents aged 8 years and older, the initial dose 15 mg/kg/day PO in 3 divided doses. Serum concentrations were measured after 1 week, and the dose was titrated until serum concentration was 7 to 10 mcg/mL. Clinical pediatric guideline algorithms include a recommendation of carbamazepine as one choice for first line monotherapy (Stage 1) treatment of nonpsychotic bipolar disorder I (manic or mixed) in pediatric patients 6 to 17 years of age. Other first line agents include: valproate, lithium, olanzapine, quetiapine, and risperidone. Both the clinical experience of the provider and the side effect profile of the medication for a given child must guide initial monotherapy selection. The panel recommended a minimum of 4 to 6 weeks at therapeutic blood levels and/or adequate dose for carbamazepine to assess initial response. In children with psychosis, combination therapy with a mood stabilizer, such as carbamazepine, and an atypical antipsychotic is suggested. Additional recommendations based on response to initial monotherapy and augmentation strategies can be found within the guideline and accompanying algorithms.

    Oral dosage (extended-release capsules, Equetro)
    Adults

    Initially, 200 mg PO twice a day. Adjust dose in 200 mg/day increments to achieve optimal clinical response. Max: 1600 mg/day PO, in divided doses twice daily. Long-term maintenance is appropriate in most patients with bipolar disorder. Periodically assess the need for continued therapy. Effectiveness as monotherapy was established in 2 (3 week) multicenter, randomized, double-blind, flexible dose, placebo controlled studies. In both studies, patients were titrated to a dose range of 400 to 1600 mg/day divided into twice daily dosing. The mean final dose was 952 mg/day in the first study, and 726 mg/day in the second. The primary outcome was a change from baseline in the Young Mania Rating Scale (YMRS) total score. In both studies, treatment was significantly more effective than placebo in YMRS total score reduction.

    For the treatment of severe behavioral or psychological symptoms of dementia† (BPSD).
    Oral dosage (immediate-release)
    Adults

    Initially, 100 mg/day PO (usually given as 50 mg PO twice daily for immediate-release tablets or 25 mg PO 4 times per day for oral suspension). May gradually increase the daily dose (e.g., adjust every 3 to 7 days) according to response and tolerability. Mean effective total daily dose range after titration: 200 mg/day to 400 mg/day PO given in 2 to 4 divided doses per clinical trials; mean effective target carbamazepine serum concentrations were within the normal therapeutic range (e.g., mean concentration approx. 5 mcg/mL). In a 6-week, placebo-controlled, double-blind trial, carbamazepine showed significant improvement over placebo for the mean change in total Brief Psychiatric Rating Scale (BPRS) sub-item scores for Hostility and Agitation but not other BPRS sub-items, in patients with agitation and aggression associated with various types of dementia (n = 51). In this study, carbamazepine was initially dosed at 100 mg/day and increased by 50 mg/day every 2 to 4 days unless there were side effects. The mean total daily dose of carbamazepine at week 6 was 304 +/- 119 mg/day and the mean serum concentration was 5.3 mcg/mL (range: 3.5 to 7.6 mcg/mL). Carbamazepine also showed significant improvement over placebo on the Overt Aggression Scale score and the Behavior Rating Scale for Dementia score. In a separate placebo-controlled trial beginning with 100 mg/day and titration up to 100 mg PO 4 times daily in patients with possible or probable Alzheimer's disease, carbamazepine showed significant improvement over placebo on the BPRS Hostility sub-item, the Hamilton Depression Rating Scale score, and the Physical Self Maintenance Scale (PSMS) score. The mean total daily dose was 388 +/- 44 mg/day and the mean serum concentration was 4.9 mcg/mL (range: 3.7 to 6.8 mcg/mL). Of note, on the Hallucination sub item, carbamazepine-treated subjects worsened and placebo-treated subjects showed no change.

    For the treatment of persistent singultus (hiccups)†.
    Oral dosage (regular-release tablets)
    Adults

    200 mg PO three times per day provided relief of intractable hiccups secondary to new-onset multiple sclerosis.

    For long-term prophylaxis of short-lasting short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)†.
    Oral dosage (regular-release tablets or suspension)
    Adults

    A limited number of case reports suggest doses of 600 to 1200 mg PO once daily may be effective. Some patients used carbamazepine in combination with other drugs including prednisolone or lamotrigine.

    †Indicates off-label use

    MAXIMUM DOSAGE

    As with all anticonvulsant-type medications, carbamazepine dosage must be individualized.

    Adults

    Oral formulations: 1200 mg/day PO for trigeminal neuralgia. In rare instances, 1600 mg/day PO for epilepsy or bipolar disorder.
    IV formulation: 1120 mg/day IV for epilepsy.

    Geriatric

    Oral formulations: 1200 mg/day PO for trigeminal neuralgia. In rare instances, 1600 mg/day PO for epilepsy or bipolar disorder.
    IV formulation: 1120 mg/day IV for epilepsy.

    Adolescents

    Oral formulations:
    16 years or older: 1200 mg/day PO for epilepsy.
    13 to 15 years: 1000 mg/day PO for epilepsy.

    Children

    Immediate-release formulations, extended-release tablets:
    6 to 12 years: 1000 mg/day PO for epilepsy.
    5 years or younger: 35 mg/kg/day PO for epilepsy.
    Extended-release capsules:
    12 years or younger: 35 mg/kg/day PO for epilepsy.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Consider dosage reductions in patients with hepatic impairment. If newly occurring or worsening clinical or laboratory evidence of liver dysfunction or hepatic damage occurs during carbamazepine treatment, consider discontinuation.

    Renal Impairment

    Oral formulations: Specific guidelines for dosage adjustments in renal impairment are not available; it appears no dosage adjustments are needed.
    IV formulation: Use is not recommended in patients with moderate or severe renal impairment (creatinine clearance 30 to 59 mL/minute and 15 to 29 mL/minute, respectively). No dosage adjustment is necessary for patients with mild renal impairment; however, close monitoring of renal function is recommended.

    ADMINISTRATION

    Oral Administration

    Administer with meals to minimize GI side effects.

    Oral Solid Formulations

    Chewable tablets: Chew well before swallowing.
    Extended-release tablets (Tegretol XR): Swallow whole. Do not crush, cut, or chew. Damaged tablets or tablets without a release portal should not be consumed. The tablet-coating is not absorbed and is excreted in the feces; these coatings may be noticeable in the stool.
    Extended-release capsules (Carbatrol; Equetro): The capsule may be opened and the beads sprinkled over food, such as a teaspoon of applesauce or other similar food product, if desired. Do not crush or chew Carbatrol or Equetro capsules or the capsule beads. Equetro is a multi-component capsule formulation consisting of 3 different types of beads: immediate-release, extended-release, and enteric-release beads.

    Oral Liquid Formulations

    Suspension: Shake suspension well prior to use. Measure dose with calibrated oral syringe, spoon, or cup.
    For administration of suspension via nasogastric or enteral feeding tubes: To minimize any interaction that might occur with enteral feedings, turn off feedings at least 15 minutes before and hold for 15 minutes after the administration of a dose. Before drug administration, flush the tube with 15 to 30 mL (adults) of water, 5% Dextrose Injection, or 0.9% Sodium Chloride Injection. To minimize the loss of drug, dilute the suspension with an equal volume of water prior to administration. After administration, flush the tube with an additional 15 to 30 mL (adults) of water, 5% Dextrose Injection, or 0.9% Sodium Chloride Injection. Do not administer carbamazepine suspension with any other liquid medications or diluents.
    For conversion from oral tablets/capsules to oral suspension: Since a given dose of carbamazepine suspension will produce higher peak concentrations than the same dose given as tablets or capsules, patients should be converted to the suspension from the oral tablets or capsules by administering the same number of mg per day in smaller, more frequent doses (e.g., changing from twice per day for tablets to 4 times per day for the suspension).

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Prepare the solution for each infusion by transferring the single dose volume of the drug to 100 mL of diluent solution (0.9% Sodium Chloride Injection, Lactated Ringer's Injection, or 5% Dextrose Injection, and mix gently.
    Infuse over 30 minutes.
    Storage: Discard unused vial contents. Prepared solution may be stored for a maximum of 4 hours at 20 to 25 degrees C (68 to 77 degrees F) or a maximum of 24 hours if refrigerated at 2 to 8 degrees C (36 to 46 degrees F).

    STORAGE

    Carbatrol:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Epitol :
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a dry place
    Equetro:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Tegretol:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a dry place
    Tegretol -XR:
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Carbamazepine may decrease thyroid function pharmacodynamically as has been reported with other anticonvulsants; however, the true clinical significance of this effect is not known.

    Asian patients, serious rash

    Carbamazepine may cause life-threatening serious rash, including Stevens-Johnson syndrome and toxic epidermal necrolysis. The estimated risk of developing these serious adverse effects is about 1 to 6 per 10,000 new users of carbamazepine in countries of mainly Caucasian populations, and an estimated risk which is 10 times higher in some Asian countries. The inherited variant of an immune system gene (HLA-B 1502), which is associated with the development of some serious skin reactions, is most prevalent in Asians. Therefore, it is recommended that Asian patients undergo a genetic blood test prior to initiation of carbamazepine treatment. The benefits of treatment with carbamazepine should be weighed against the risks in patients who test positive for HLA-B 1502. The test does not appear to be beneficial in those who have been taking carbamazepine for more than a few months, since it is unlikely that the skin reactions will develop after that time regardless of the presence or absence of the variant gene.

    Depression, psychosis, suicidal ideation

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

    Atonic seizures, myoclonic seizures, petit mal (absence) seizures

    Carbamazepine is not recommended for use in petit mal (absence) seizures, atonic seizures, or myoclonic seizures because it can exacerbate these conditions. If a worsening of seizures occurs when therapy is initiated, this possibility should be considered.

    Abrupt discontinuation

    Unless severe adverse reactions warrant, abrupt discontinuation of carbamazepine therapy should not be undertaken in patients with seizure disorders. Anticonvulsant drugs should be withdrawn gradually to minimize the potential of increased seizure frequency. If adverse reactions are of such severity that carbamazepine must be discontinued, the practitioner must be aware that abrupt discontinuation of any anticonvulsant drug in a responsive epileptic patient may lead to drug withdrawal seizures or even status epilepticus with its life-threatening hazards.

    Barbiturate hypersensitivity, carbamazepine hypersensitivity, fever, hydantoin hypersensitivity, jaundice, tricyclic antidepressant hypersensitivity

    Carbamazepine is contraindicated in patients with a carbamazepine hypersensitivity. Carbamazepine is structurally related to tricyclic antidepressants, and is contraindicated in patients with a tricyclic antidepressant hypersensitivity. Carbamazepine therapy should be prescribed only after critical benefit-to-risk assessment in patients with a history of adverse hematologic, hypersensitivity, adverse reactions to carbamazepine, or other anticonvulsants, and in patients known to be positive for HLA-A 3101. There is a moderate association between the risk of developing hypersensitivity reactions and the presence of HLA-A 3101, an inherited allelic variant of the HLA-A gene. HLA-A 3101 is expected to be carried by > 15% of patients of Japanese, Native American, Southern Indian and some Arabic ancestry; up to about 10% in patients of Han Chinese, Korean, European, Latin American, and other Indian ancestry; and up to about 5% in African-Americans and patients of Thai, Taiwanese, and Chinese ancestry. Hypersensitivity reactions to anticonvulsants may present as various organ system problems, including cardiac, liver, renal, and skin disorders. A history of hypersensitivity reactions should be obtained for a patient and the immediate family members. If hypersensitivity histories are positive to other classes of anticonvulsants, caution should be used in prescribing carbamazepine. Hypersensitivity reactions to carbamazepine have been reported in patients who previously experienced hydantoin hypersensitivity (i.e., fosphenytoin, phenytoin) or barbiturate hypersensitivity (i.e., hypersensitivity to phenobarbital or primidone). Estimates of cross-sensitivity vary, but may range from 30—80%. Carbamazepine, hydantoins, and phenobarbital are all metabolized to hydroxylated aromatic compounds via the cytochrome P450 hepatic oxidative enzymes; arene oxide intermediates are formed during metabolism and are thought to be responsible for cross-sensitivity among these anticonvulsants in susceptible individuals. Cross-sensitivity has also been noted between oxcarbazepine and carbamazepine. Some individuals may have a reduced ability to detoxify the intermediate toxic metabolites (e.g., arene oxides) of these anticonvulsants, which may be genetically mediated. However, studies of familial reactions have also shown that allergies to one anticonvulsant may not translate to allergies to others. There is no way to predict with certainty which patients will exhibit cross-sensitivity. Therefore, patients should be made aware of the early signs and symptoms of a potential hematological problem, as well as dermatological, hypersensitivity, or hepatic reactions. These symptoms may include, but are not limited to, fever, sore throat, rash, ulcers in the mouth, easy bruising, lymphadenopathy and petechial or purpuric hemorrhage, and in the case of liver reactions, anorexia, nausea/vomiting, or jaundice. The patient should be advised that, because these signs and symptoms may signal a serious reaction, that they must report any occurrence immediately to a physician. In addition, the patient should be advised that these signs and symptoms should be reported even if mild or occurring after extended use.

    Agranulocytosis, aplastic anemia, bone marrow suppression, hematological disease, leukopenia, neutropenia, thrombocytopenia

    Carbamazepine is contraindicated in patients with a history of bone marrow suppression. Carbamazepine should be used with caution in patients with blood dyscrasias caused by drug therapies or hematological disease because of the potential increased risk of hematologic toxicity. Although uncommon, carbamazepine can cause hematological toxicity consisting of transient leukopenia, neutropenia, thrombocytopenia, or more severe reactions like agranulocytosis or aplastic anemia. Case-control population data have demonstrated that the risk of developing these reactions is 5—8 times greater in patients treated with carbamazepine than in the general population. However aplastic anemia and agranulocytosis are rare in the untreated general population (i.e., 1—2 persons per one million population per year). It would be uncommon for a patient who is taking carbamazepine to develop a severe blood dyscrasia, even if hematologic changes occur during treatment. Pretreatment baseline hematologic counts should be obtained. Periodic hematologic testing during treatment is recommended; if a patient develops neutropenia or thrombocytopenia the patient should be closely monitored. Discontinuation of carbamazepine should be considered if significant bone marrow suppression develops.

    Porphyria

    Avoid use of carbamazepine in patients with a history of hepatic porphyria (e.g., acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda). Exacerbation of the condition (i.e., acute attacks) has been reported in such patients receiving carbamazepine therapy. In addition, increased porphyrin precursors in rodents, a presumed mechanism for the induction of acute attacks of porphyria, have been demonstrated following carbamazepine administration.

    Hepatic disease

    Carbamazepine should be used with caution in patients with hepatic disease because the drug is metabolized in the liver. Carbamazepine hepatotoxicity also has been reported. Hepatotoxicity may be associated with jaundice, rash and eosinophilia. Liver toxicity may be the result of hypersensitivity to the drug. Baseline and periodic evaluations of liver function, particularly in patients with a history of liver disease, must be performed during treatment with this drug since liver damage may occur. Carbamazepine should be discontinued, based on clinical judgment, if indicated by newly occurring or worsening clinical or laboratory evidence of liver dysfunction or hepatic damage, or in the case of active hepatic disease.

    AV block, bundle-branch block, cardiac arrhythmias, cardiac disease, coronary artery disease

    Carbamazepine should be used with caution in any patient with cardiac disease, such as cardiac arrhythmias, congestive heart failure or coronary artery disease, because symptoms may be potentiated or exacerbated. Second and third degree heart block have been reported during use of the drug, primarily in patients with pre-existing EKG abnormalities or risk factors for conduction disturbances. Carbamazepine should be avoided if possible in patients with AV block or other conduction abnormalities (bundle-branch block). Myocardial infarction has been associated with other tricyclic compounds (e.g., amitriptyline).

    Hyponatremia

    Hyponatremia may develop during treatment with carbamazepine. Hyponatremia may be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH risk with carbamazepine treatment appears to be dose-related. Elderly patients and patients receiving diuretic therapy are at greater risk for developing hyponatremia. Consider discontinuation of carbamazepine in patients who develop signs or symptoms of symptomatic hyponatremia (e.g., headache, new or increased seizure frequency, concentration difficulty, memory impairment, confusion, weakness, or unsteadiness). Consider monitoring sodium concentrations if clinically appropriate.

    Alcoholism

    Carbamazepine should be used with caution in patients with alcoholism because they can experience increased CNS depression and have an increased risk for hepatotoxicity. In addition, concomitant use of carbamazepine and ethanol can decrease the ability to perform tasks requiring mental alertness.

    Driving or operating machinery

    Carbamazepine commonly causes blurred vision, dizziness, drowsiness, and fatigue. Patients should be advised to use caution when driving or operating machinery, or performing other tasks that require mental alertness until they are aware of whether carbamazepine adversely affects their mental and/or motor performance.

    Renal disease, renal failure, renal impairment

    Carbamazepine may rarely cause interstitial nephritis or other renal disease. Due to the potential for renal toxicity, baseline and periodic complete urinalysis and BUN tests are recommended for patients treated with carbamazepine. Intravenous carbamazepine should not be used in patients with moderate or severe renal failure or impairment (creatinine clearance 30 to 59 mL/minute and 15 to 29 mL/minute, respectively) because of the potential for accumulation of sulfobutylether beta-cyclodextrin sodium salt. There is a greater risk for adverse renal effects with salt accumulation. No dosage adjustment is recommended in patients with mild renal impairment; however, close monitoring of renal function is advised.

    Geriatric

    Geriatric patients may be more susceptible to confusion or agitation, cardiac side effects, or syndrome of inappropriate antidiuretic hormone (SIADH) secondary to carbamazepine treatment.[41237] According to the Beers Criteria, anticonvulsants are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures. Avoid in at-risk patients except for treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If carbamazepine must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk. The Beers panel recommends caution when using carbamazepine in older adults because the drug can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions. Sodium levels should be closely monitored when starting or changing dosages in older adults.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities; the use of any anticonvulsant for any condition should be based on confirmation of the condition and its potential cause(s). Determine effectiveness and tolerability by evaluating symptoms, and use these as the basis for dosage adjustment for most patients. Therapeutic drug monitoring is available for carbamazepine and periodic serum concentrations should be monitored as clinically indicated. Serum medication concentrations (when available) may assist in identifying toxicity. High or toxic serum concentrations should become a consideration for dosage adjustments. Monitor the treated patient for drug efficacy and side effects. Carbamazepine can cause liver dysfunction, blood dyscrasias, and serious skin rashes requiring discontinuation of treatment. Anticonvulsants can cause a variety of other side effects; some adverse reactions can increase the risk of falls. When an anticonvulsant is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity as outlined in the OBRA guidelines.[60742]

    Glaucoma, increased intraocular pressure

    Carbamazepine exhibits mild anticholinergic activity and should be used with caution in glaucoma or other conditions associated with increased intraocular pressure. Baseline and periodic eye examinations, including slit-lamp, funduscopy, and tonometry, are recommended.

    Pregnancy

    Carbamazepine can cause fetal harm when administered during pregnancy. Pregnancy registry and epidemiological data demonstrate an association between carbamazepine use during pregnancy and congenital malformations, including spina bifida, craniofacial defects, and cardiovascular malformations. Women of child-bearing potential should be informed of the potential risk to the fetus, and patients should be instructed to contact their physician immediately if they become pregnant or intend to become pregnant. If the risk of recurrent seizures is acceptable, discontinuation of carbamazepine during pregnancy could be considered. Maintenance of anticonvulsant therapy, however, may be essential for the mother. Sudden discontinuation of therapy may result in seizures and present a significant risk to fetus and mother. Conduct tests using currently accepted procedures to detect defects during pregnancy. Folic acid supplementation prior to and during pregnancy may decrease the risk of neural tube defects in the fetus. Physicians are advised to recommend that pregnant patients receiving carbamazepine enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry to provide information about the effects of in utero exposure to the drug. Patients must call 1-888-233-2334 to enroll in the registry. In humans, transplacental passage of carbamazepine is rapid (30 to 60 minutes), and the drug is accumulated in the fetal tissues, with higher concentrations found in liver and kidney than in brain and lung. The NAAED Pregnancy Registry has reported a rate of major congential malformations of 3% (95% CI: 2.1, 4.2) among approximately 1,000 women exposed to carbamazepine monotherapy during the first trimester with a relative risk of 2.7 (95% CI: 1, 7) compared to pregnant woman not taking an antiepileptic drug. Cases of developmental delays based on neurobehavioral assessments have been reported during post-marketing experience. Compared with monotherapy, there may be a higher prevalence of teratogenic effects associated with the use of anticonvulsants in combination therapy. In a prospective, multi-center, long-term, observational study (n = 333) of fetal death and malformations during in utero exposure to monotherapy with phenytoin, carbamazepine, lamotrigine, or valproate, 8.2% of patients who received carbamazepine experienced serious adverse outcomes (fetal death or major congential abnormalities). Serious adverse outcomes occurred in 1% of lamotrigine-treated patients, 10.7% of phenytoin-treated patients, and 20.3% of valproate-treated patients. Fetal deaths occurred for 3.6% and congenital malformations for 4.5% of carbamazepine-treated patients. Congenital malformations in the carbamazepine group included absent kidney, duplicate renal pelvis, hypospadias, and inguinal hernia. The effects of carbamazepine during labor and delivery are unknown.

    Neonates

    There have been a few cases of seizures and/or respiratory depression reported in neonates; the events were associated with the maternal use of carbamazepine or other anticonvulsants close to term. A few cases of neonatal vomiting, diarrhea, and/or decreased feeding have also been reported in association with maternal anticonvulsants used during pregnancy. These symptoms may represent a neonatal withdrawal syndrome.

    Breast-feeding

    Carbamazepine and its epoxide metabolite are transferred to breast milk. The ratio of the concentration in breast milk to that in maternal plasma is about 0.4 for carbamazepine and about 0.5 for the epoxide. The estimated doses given to the newborn during breast-feeding are in the ranges of 2 to 5 mg daily for carbamazepine and 1 to 2 mg daily for the epoxide. Because of the potential for serious adverse events in a breast-fed infant exposed to carbamazepine, a decision should be made whether to discontinue breast-feeding or to discontinue carbamazepine, considering the importance of the drug to the mother. Previous American Academy of Pediatrics recommendations considered carbamazepine to be usually compatible for use during breast-feeding. Although most infants exposed to carbamazepine via breast milk have not suffered adverse events, there have been cases of transient cholestatic hepatitis in infants exposed to maternal carbamazepine monotherapy at doses of 400 to 600 mg/day throughout pregnancy and breast-feeding. Other causes of hepatitis were ruled out; resolution of symptoms in 1 infant occurred upon discontinuation of breast-feeding and in 1 infant despite breast-feeding being continued.

    Sunlight (UV) exposure

    Patients may be more prone to sunburn during therapy with carbamazepine. Suitable precautions should be taken prior to sunlight (UV) exposure, such as wearing long-sleeved clothing and a hat, and using sunscreens.

    MAOI therapy

    Carbamazepine is contraindicated in patients receiving MAOI therapy or who have received an MAOI within the previous 14 days.

    Hypercholesterolemia

    Use carbamazepine with caution in patients with preexisting hypercholesterolemia. Increases in total cholesterol, HDL, and LDL have been reported in patients receiving anticonvulsants. Periodic evaluation of cholesterol concentrations is recommended.

    ADVERSE REACTIONS

    Severe

    atrial tachycardia / Early / 0-2.0
    suicidal ideation / Delayed / 0-1.0
    neuroleptic malignant syndrome / Delayed / 0-1.0
    hepatic failure / Delayed / 0-1.0
    aplastic anemia / Delayed / 0-1.0
    agranulocytosis / Delayed / 0-1.0
    aseptic meningitis / Delayed / 0-1.0
    porphyria / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    thromboembolism / Delayed / Incidence not known
    AV block / Early / Incidence not known
    heart failure / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    erythema nodosum / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    oliguria / Early / Incidence not known
    teratogenesis / Delayed / Incidence not known
    ocular hypertension / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known

    Moderate

    constipation / Delayed / 10.0-10.0
    blurred vision / Early / 5.0-6.0
    hypertension / Early / 3.0-3.0
    hyponatremia / Delayed / 0-2.0
    anemia / Delayed / 2.0-2.0
    infusion-related reactions / Rapid / 2.0-2.0
    leukopenia / Delayed / 0-1.0
    eosinophilia / Delayed / 0-1.0
    thrombocytopenia / Delayed / 0-1.0
    ataxia / Delayed / 10.0
    depression / Delayed / Incidence not known
    confusion / Early / Incidence not known
    hallucinations / Early / Incidence not known
    neuritis / Delayed / Incidence not known
    hyperacusis / Delayed / Incidence not known
    nystagmus / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    osteoporosis / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    edema / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    Onychomadesis / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    hypertriglyceridemia / Delayed / Incidence not known
    glycosuria / Early / Incidence not known
    urinary retention / Early / Incidence not known
    proteinuria / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    glossitis / Early / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    vitamin D deficiency / Delayed / Incidence not known
    folate deficiency / Delayed / Incidence not known

    Mild

    dizziness / Early / 1.0-10.0
    pruritus / Rapid / 8.0-8.0
    xerostomia / Early / 8.0-8.0
    asthenia / Delayed / 8.0-8.0
    rash / Early / 7.0-7.0
    diplopia / Early / 4.0-4.0
    tremor / Early / 3.0-3.0
    headache / Early / 3.0-3.0
    paresthesias / Delayed / 2.0-2.0
    vertigo / Early / 2.0-2.0
    leukocytosis / Delayed / 0-1.0
    nausea / Early / 10.0
    vomiting / Early / 10.0
    drowsiness / Early / 10.0
    tinnitus / Delayed / Incidence not known
    fatigue / Early / Incidence not known
    agitation / Early / Incidence not known
    syncope / Early / Incidence not known
    alopecia / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    hirsutism / Delayed / Incidence not known
    diaphoresis / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    increased urinary frequency / Early / Incidence not known
    diarrhea / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    abdominal pain / Early / Incidence not known
    muscle cramps / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Major) When possible, avoid concurrent use of dolutegravir with carbamazepine in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive patients or treatment-experienced but INSTI-naive patients who weigh at least 40 kg, the dose of dolutegravir should be increased to 50 mg PO twice daily when administered with carbamazepine. For pediatric patients weighing 30 to 39 kg, the FDA-approved product labeling recommends increasing the dose of dolutegravir to 35 mg PO twice daily if administered concurrently with carbamazepine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Predictions regarding this interaction can be made based on the drugs metabolic pathways. Carbamazepine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Abemaciclib: (Major) Avoid coadministration of carbamazepine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
    Abiraterone: (Major) Avoid coadministration of abiraterone with carbamazepine if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if carbamazepine is discontinued. Abiraterone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
    Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and carbamazepine. If coadministration cannot be avoided, increase the acalabrutinib dose to 200 mg PO twice daily. Decreased acalabrutinib exposure may occur. Acalabrutinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. In healthy subjects, the Cmax and AUC values of acalabrutinib were decreased by 68% and 77%, respectively, when acalabrutinib was coadministered with another strong CYP3A4 inducer for 9 days.
    Acetaminophen: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Butalbital: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Caffeine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with carbamazepine 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 carbamazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Carbamazepine is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Dextromethorphan: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Diphenhydramine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Guaifenesin; Phenylephrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of oxycodone as needed. If carbamazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Pentazocine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Propoxyphene: (Moderate) Monitor for reduced efficacy of propoxyphene and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of propoxyphene as needed. If carbamazepine is discontinued, consider a dose reduction of propoxyphene and frequently monitor for signs or respiratory depression and sedation. Propoxyphene is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease propoxyphene levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Pseudoephedrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetaminophen; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of tramadol as needed. If carbamazepine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Acetazolamide: (Minor) Acetazolamide can induce osteomalacia in patients being concomitantly treated with carbamazepine. Potential mechanisms for this interaction include an acetazolamide-induced increase in the urinary excretion of calcium and effects resulting from metabolic acidosis.
    Adenosine: (Major) Carbamazepine can increase the degree of heart block precipitated by other cardioactive agents including adenosine.
    Afatinib: (Major) Increase the daily dose of afatinib by 10 mg as tolerated if the concomitant use with carbamazepine is necessary; resume the previous dose of afatinib 2 to 3 days after discontinuation of carbamazepine. Afatinib is a P-glycoprotein (P-gp) substrate and carbamazepine is a P-gp inducer; coadministration may decrease plasma concentrations of afatinib. Pre-treatment with another strong P-gp inducer decreased afatinib exposure by 34%.
    Albendazole: (Minor) Enzyme-inducing antiepileptic drugs, such as carbamazepine, appear to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. Monitor patient clinical response closely during treatment.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity (e.g., mood stabilizing agents, like carbamazepine). Use with caution. Patients developing mood disturbances, moderate to severe lethargy/somnolence while on aldesleukin should seek evaluation from their health care provider. In addition, aldesleukin has significant thrombocytopenic effects and may possess hematologic toxicities similar to carbamazepine. Use together with caution and monitor blood counts as appropriate.
    Alfentanil: (Moderate) Monitor for reduced efficacy of alfentanil and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of alfentanil as needed. If carbamazepine is discontinued, consider a dose reduction of alfentanil and frequently monitor for signs or respiratory depression and sedation. Alfentanil is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease alfentanil levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Aliskiren; Amlodipine: (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia. (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Alosetron: (Minor) Alosetron is metabolized by CYP1A2 and CYP3A4. Carbamazepine can induce the activity of these enzymes and increase the metabolism of alosetron. Concomitant administration of carbamazepine and alosetron has not been evaluated.
    Alpelisib: (Major) Avoid coadministration of alpelisib with carbamazepine due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer.
    Alprazolam: (Moderate) Carbamazepine is a hepatic enzyme inducer and may potentially accelerate the hepatic metabolism of alprazolam leading to lower alprazolam serum concentrations. Concomitant administration of alprazolam with CNS-depressant drugs, including anticonvulsants, can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Altretamine: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Amiodarone: (Moderate) Adjust amiodarone and carbamazepine doses as needed based on efficacy and tolerability. Consider monitoring amiodarone serum concentrations during concurrent use. Coadministration of amiodarone and carbamazepine may result in decreased amiodarone exposure and/or increased carbamazepine exposure. Carbamazepine is a CYP3A4 substrate and strong CYP3A4 inducer; amiodarone is a CYP3A4 substrate and moderate CYP3A4 inhibitor.
    Amitriptyline; Chlordiazepoxide: (Moderate) Hepatic inducers, such as carbamazepine, can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Amlodipine: (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Atorvastatin: (Moderate) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, such as atorvastatin. (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Benazepril: (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia. (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia. (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Olmesartan: (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Telmisartan: (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amlodipine; Valsartan: (Moderate) Monitor for increased carbamazepine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability. The dosage requirements of amlodipine may be increased in patients receiving concurrent enzyme inducers.
    Amobarbital: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Coadministration of carbamazepine 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. Additionally, carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as clarithromycin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely during coadministration; reduce carbamazepine doses may be necessary. Clarithromycin also inhibits epoxide hydrolase resulting in increased levels of the active metabolite carbamazepine 10, 11- epoxide, which may be more hepatotoxic than the parent drug. Several case reports have documented that clarithromycin can significantly decrease carbamazepine clearance, producing increases in the serum concentration of carbamazepine. Carbamazepine concentrations increased from 12 mcg/ml to 19.1 mcg/ml in a 17-year-old boy after 2 days of clarithromycin 250 mg PO bid. Patients should be monitored for carbamazepine toxicity if clarithromycin is added. Carbamazepine toxicity may be avoided if clarithromycin therapy is begun first and stabilized prior to beginning carbamazepine therapy, however, carbamazepine dosages may need to be increased if clarithromycin is subsequently discontinued. (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Carbamazepine induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of carbamazepine 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. Additionally, carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as clarithromycin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely during coadministration; reduce carbamazepine doses may be necessary. Clarithromycin also inhibits epoxide hydrolase resulting in increased levels of the active metabolite carbamazepine 10, 11- epoxide, which may be more hepatotoxic than the parent drug. Several case reports have documented that clarithromycin can significantly decrease carbamazepine clearance, producing increases in the serum concentration of carbamazepine. Carbamazepine concentrations increased from 12 mcg/ml to 19.1 mcg/ml in a 17-year-old boy after 2 days of clarithromycin 250 mg PO bid. Patients should be monitored for carbamazepine toxicity if clarithromycin is added. Carbamazepine toxicity may be avoided if clarithromycin therapy is begun first and stabilized prior to beginning carbamazepine therapy, however, carbamazepine dosages may need to be increased if clarithromycin is subsequently discontinued. (Moderate) Omeprazole may increase the Cmax, AUC, and elimination half-life of carbamazepine when given as an extended-release formulation. Monitor carbamazepine serum concentrations when omeprazole is added to the drug regimen.
    Amphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Amphetamine; Dextroamphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Amphetamines: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Amprenavir: (Major) Carbamazepine may increase the metabolism of amprenavir and lead to decreased efficacy of amprenavir. If amprenavir is added to anticonvulsant therapy, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or seizure control.
    Anagrelide: (Moderate) Anagrelide is partially metabolized by CYP1A2. Coadministration of anagrelide with drugs that induce CYP1A2, such as carbamazepine, could theoretically increase the elimination of anagrelide and decrease its efficacy. Patients should be monitored for changes in efficacy if these drugs are coadministered.
    Antimetabolites: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Antitumor antibiotics: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Apalutamide: (Moderate) Closely monitor carbamazepine levels if coadministration with apalutamide is necessary. Carbamazepine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Inducers of CYP3A4 can increase the rate of carbamazepine metabolism and decrease carbamazepine levels.
    Apixaban: (Major) Avoid the concomitant administration of apixaban and drugs that are both strong inducers of CYP3A4 and P-gp, such as carbamazepine. Concomitant administration of apixaban and carbamazepine results in decreased plasma concentrations of apixaban that may be insufficient to achieve the intended therapeutic effect.
    Apremilast: (Major) The coadministration of apremilast and carbamazepine is not recommended. Apremilast is metabolized primarily by CYP3A4, with minor metabolism by CYP1A2. Carbamazepine is a strong CYP3A4 inducer and also induces CYP1A2. Coadministration of rifampin, another strong CYP3A4 inducer, with a single dose of apremilast resulted in a decrease in apremilast AUC and Cmax by 72% and 43%, respectively. A similar reduction in systemic exposure may be seen with coadministration of apremilast and carbamazepine which may result in a loss of efficacy of apremilast.
    Aprepitant, Fosaprepitant: (Major) Avoid the concurrent use of carbamazepine with aprepitant, fosaprepitant due to substantially decreased exposure of aprepitant. If these drugs must be coadministered, monitor for a decrease in the efficacy of aprepitant as well as an increase in carbamazepine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Carbamazepine is a strong CYP3A4 inducer and aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen (a strong CYP3A4 inducer), the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold. Additionally, carbamazepine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may also increase plasma concentrations of carbamazepine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Aripiprazole: (Major) Because aripiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when a potent CYP3A4 inducer, such as carbamazepine, is added to aripiprazole therapy. Concurrent use of carbamazepine (200 mg twice daily) and aripiprazole (30 mg/day) resulted in a decrease in Cmax and AUC values of aripiprazole and its active metabolite by about 70%. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is discontinued, the oral aripiprazole dose should be reduced to the original level over 1 to 2 weeks. Avoid concurrent use of Abilify Maintena with a strong CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving Aristada with a strong CYP3A4 inducer, no dose adjustment is necessary for the 662 mg, 882 mg, or 1,064 mg dose; increase the 441 mg dose to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers.
    Armodafinil: (Moderate) Armodafinil is partially metabolized by CYP3A4 and combined use with CYP3A4 inducers such as carbamazepine may result in decreased armodafinil efficacy. In vitro data indicate that armodafinil is an inducer of CYP3A4. Therefore, decreased carbamazepine serum levels are possible during combined use with armodafinil. Clinically, be alert for increased sleepiness or other indicators of reduced armofafinil efficacy. The potential pharmacodynamic effects of combining armodafinil with anticonvulsant medications are unclear; however, should it be noted that other CNS stimulants (e.g., amphetamines) are known to lower the seizure threshold.
    Arsenic Trioxide: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Artemether; Lumefantrine: (Severe) Concomitant use of carbamazepine and artemether; lumefantrine is contraindicated. Carbamazepine is a substrate/inducer of CYP3A4 and both components of artemether; lumefantrine are substrates of this isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations and possible reduction in antimalarial activity.
    Asenapine: (Moderate) Drugs that can cause significant CNS effects such as drowsiness and dizziness, such as carbamazepine, if used concomitantly with asenapine, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Carbamazepine has been tested and has been found to have no clinically significant pharmacokinetic interaction with asenapine; no dosage adjustment is necessary based on pharmacokinetics.
    Asparaginase Erwinia chrysanthemi: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with carbamazepine 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 carbamazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Carbamazepine is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
    Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
    Aspirin, ASA; Omeprazole: (Moderate) Omeprazole may increase the Cmax, AUC, and elimination half-life of carbamazepine when given as an extended-release formulation. Monitor carbamazepine serum concentrations when omeprazole is added to the drug regimen.
    Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of oxycodone as needed. If carbamazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Atazanavir: (Major) Coadministration of carbamazepine and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. Avoid coadministration of atazanavir with carbamazepine unless atazanavir is boosted with ritonavir. In addition, coadministration of atazanavir and ritonavir with carbamazepine may result in increased carbamazepine concentrations. If atazanavir and carbamazepine are used together, the patient must be closely monitored for antiviral efficacy and carbamazepine toxicity; clinical monitoring of carbamazepine concentrations with dosage titration if necessary is also warranted.
    Atazanavir; Cobicistat: (Severe) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Coadministration of carbamazepine and atazanavir may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance. Avoid coadministration of atazanavir with carbamazepine unless atazanavir is boosted with ritonavir. In addition, coadministration of atazanavir and ritonavir with carbamazepine may result in increased carbamazepine concentrations. If atazanavir and carbamazepine are used together, the patient must be closely monitored for antiviral efficacy and carbamazepine toxicity; clinical monitoring of carbamazepine concentrations with dosage titration if necessary is also warranted.
    Atenolol; Chlorthalidone: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Atorvastatin: (Moderate) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, such as atorvastatin.
    Atorvastatin; Ezetimibe: (Moderate) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, such as atorvastatin.
    Atracurium: (Moderate) If neuromuscular blockers are administered to patients chronically receiving anticonvulsant agents such as carbamazepine, shorter durations of neuromuscular block may occur and infusion rates may be higher due to the development of resistance to muscle relaxants.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
    Auranofin: (Minor) Auranofin should be used cautiously in patients receiving carbamazepine, due to the potential for additive bone marrow/hematologic effects.
    Avanafil: (Minor) Avanafil is primarily metabolized by CYP3A4, and although no studies have been preformed, concomitant administration of CYP3A4 inducers, such as carbamazepine, may decrease avanafil plasma levels. Concomitant use is not recommended.
    Avatrombopag: (Major) In patients with chronic immune thrombocytopenia (ITP), increase the starting dose of avatrombopag to 40 mg PO once daily when used concomitantly with carbamazepine. In patients starting carbamazepine while receiving avatrombopag, monitor platelet counts and adjust the avatrombopag dose as necessary. Dosage adjustments are not required for patients with chronic liver disease. Avatrombopag is a CYP2C9 and CYP3A4 substrate, and dual moderate or strong inducers such as carbamazepine decrease avatrombopag exposure, which may reduce efficacy.
    Axitinib: (Major) Avoid coadministration of axitinib with carbamazepine, due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is primarily metabolized by CYP3A4. Carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4/5 inducer significantly decreased the plasma exposure of axitinib in healthy volunteers.
    Azathioprine: (Minor) Azathioprine should be used cautiously in patients receiving carbamazepine, due to the potential for additive bone marrow/hematologic effects.
    Azelastine; Fluticasone: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
    Azilsartan; Chlorthalidone: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Barbiturates: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
    Bedaquiline: (Major) Avoid concurrent use of carbamazepine with bedaquiline. Carbamazepine may induce CYP3A4 metabolism resulting in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Bendamustine: (Moderate) Use bendamustine and carbamazepine together with caution; concomitant use may result in decreased bendamustine plasma concentrations and reduced bendamustine effectiveness. Use of alternative agents should be considered. Bendamustine is metabolized by CYP1A2 to form the active metabolites, gamma-hydroxy bendamustine (M3) and N-desmethyl-bendamustine (M4); however, cytotoxic activity is primarily due to the parent bendamustine compound. CYP1A2 inducers, such as carbamazepine, may decrease plasma concentrations of bendamustine and increase plasma concentrations of its active metabolites.
    Bendroflumethiazide; Nadolol: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with carbamazepine 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 carbamazepine may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If carbamazepine is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Carbamazepine is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Benzphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Bepridil: (Moderate) Carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability of the calcium channel blockers by increasing their presystemic clearance.
    Betrixaban: (Major) Avoid the concomitant administration of betrixaban and carbamazepine. Concomitant administration of betrixaban and carbamazepine results in decreased plasma concentrations of betrixaban that may decrease efficacy. Betrixaban is a P-glycoprotein (P-gp) substrate and carbamazepine is a P-gp inducer.
    Bicalutamide: (Major) Bicalutamide is metabolized by cytochrome P450 3A4. Drugs that are potent inducers of CYP3A4 activity, such as carbamazepine, will decrease the plasma concentrations of bicalutamide. It is unknown if dosing adjustments are necessary.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Administering tenofovir alafenamide with carbamazepine 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 (Major) Consider an alternative anticonvulsant during treatment with bictegravir. Concomitant use of bictegravir and carbamazepine may result in decreased bictegravir plasma concentrations, which may result in the loss of therapeutic efficacy and development of resistance. Bictegravir is a substrate of CYP3A4; carbamazepine is a strong inducer of CYP3A4. In drug interaction studies, coadministration of bictegravir and carbamazepine decreased the mean AUC of bictegravir by approximately 54%
    Biotin: (Moderate) Carbamazepine use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like carbamazepine, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Minor) Monitor serum concentrations of carbamazepine when coadministered with systemic metronidazole. Concomitant use with metronidazole may increase the serum concentrations of carbamazepine; thereby, increasing the risk of side effects.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Monitor serum concentrations of carbamazepine when coadministered with systemic metronidazole. Concomitant use with metronidazole may increase the serum concentrations of carbamazepine; thereby, increasing the risk of side effects.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Blinatumomab: (Moderate) No drug interaction studies have been performed with blinatumomab. The drug may cause a transient release of cytokines leading to an inhibition of CYP450 enzymes. The interaction risk with CYP450 substrates is likely the highest during the first 9 days of the first cycle and the first 2 days of the second cycle. Monitor patients receiving concurrent CYP450 substrates that have a narrow therapeutic index (NTI) such as carbamazepine. The dose of the concomitant drug may need to be adjusted.
    Boceprevir: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with carbamazepine; concurrent use is contraindicated. Carbamazepine is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
    Bortezomib: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Bosentan: (Moderate) Coadministration of bosentan and carbamazepine may result in decreased plasma concentrations of both drugs; monitor for loss of therapeutic effect. Bosentan is an inducer of cytochrome P450 3A4, the major isoform responsible for carbamazepine's metabolism. If a patient is stable on carbamazepine therapy and bosentan is initiated, monitor plasma carbamazepine concentrations and clinical efficacy; a carbamazepine dosage adjustment may be necessary. Additionally, carbamazepine may theoretically decrease serum concentrations of bosentan. Carbamazepine is an inducer of both CYP2C9 and CYP3A4, the isoenzymes known to be involved in the metabolism of bosentan.
    Bosutinib: (Major) Avoid concomitant use of bosutinib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as carbamazepine, as a large decrease in bosutinib plasma exposure may occur. Carbamazepine may interact with chemotherapeutic agents by different mechanisms. Although documentation of drug-drug interactions may not always be available, myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine. Clinicians should be alert to changes in the clinical effects of these agents. If coadministration is necessary, dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
    Brentuximab vedotin: (Moderate) Concomitant administration of brentuximab vedotin and carbamazepine may decrease the exposure of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin. MMAE is a CYP3A4 substrate and carbamazepine is a potent CYP3A4 inducer; therefore, the efficacy of brentuximab may be reduced.
    Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be doubled over 1 to 2 weeks when a strong CYP3A4 inducer, such as carbamazepine, is added to brexpiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in brexpiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the brexpiprazole dose should be reduced to the original level over 1 to 2 weeks.
    Brigatinib: (Major) Avoid coadministration of brigatinib with carbamazepine due to decreased plasma exposure to brigatinib which may result in decreased efficacy. Brigatinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased the AUC and Cmax of brigatinib by 80% and 60%, respectively.
    Brivaracetam: (Moderate) Coadministration with carbamazepine may increase exposure to the active metabolite of carbamazepine, carbamazepine-epoxide, due to brivaracetam being a reversible inhibitor of epoxide hydrolase. During drug interaction studies, the carbamazepine-epoxide plasma concentration increased up to 198% with a brivaracetam dose of 100 mg twice daily. If tolerability issues arise during concomitant use, carbamazepine dose reduction should be considered. A 26% decrease in the plasma concentration of brivaracetam has also been observed during co-administration with carbamazepine. No dose adjustment is recommended for brivaracetam during concomitant carbamazepine therapy.
    Brodalumab: (Moderate) If brodalumab is initiated or discontinued in a patient taking carbamazepine, monitor carbamazepine concentrations; carbamazepine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during brodalumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as carbamazepine.
    Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and carbamazepine are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; carbamazepine is a strong inducer of CYP3A4.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Budesonide: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of budesonide. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with budesonide.
    Budesonide; Formoterol: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of budesonide. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with budesonide.
    Bupivacaine Liposomal: (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
    Bupivacaine: (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
    Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and carbamazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; carbamazepine induces both hepatic isoenzymes. (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
    Buprenorphine: (Moderate) Inducers of CYP3A4 such as carbamazepine, may induce the hepatic metabolism of buprenorphine or opiate agonists, which may lead to opiate withdrawal or inadequate pain control.
    Buprenorphine; Naloxone: (Moderate) Inducers of CYP3A4 such as carbamazepine, may induce the hepatic metabolism of buprenorphine or opiate agonists, which may lead to opiate withdrawal or inadequate pain control.
    Bupropion: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Carbamazepine induces hepatic enzymes and may lower bupropion exposure. Bupropion is a sensitive substrate of CYP2B6, and carbamazepine is a potent inducer for this enzyme. Monitor for signs of reduced bupropion efficacy during use together. Also monitor for any changes in seizure status if carbamazepine is used to treat seizures.
    Bupropion; Naltrexone: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Carbamazepine induces hepatic enzymes and may lower bupropion exposure. Bupropion is a sensitive substrate of CYP2B6, and carbamazepine is a potent inducer for this enzyme. Monitor for signs of reduced bupropion efficacy during use together. Also monitor for any changes in seizure status if carbamazepine is used to treat seizures.
    Buspirone: (Moderate) Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, like carbamazepine, may increase the rate of buspirone metabolism.
    Butabarbital: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
    Cabozantinib: (Major) Avoid coadministration of cabozantinib with carbamazepine due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with carbamazepine 2 to 3 days after discontinuation of carbamazepine. Cabozantinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
    Caffeine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
    Caffeine; Ergotamine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
    Canakinumab: (Moderate) If canakinumab is initiated or discontinued in a patient taking carbamazepine, monitor carbamazepine concentrations; carbamazepine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during canakinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as carbamazepine.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Cannabidiol: (Moderate) Consider a dose increase of cannabidiol if coadministered with carbamazepine. Coadministration may decrease cannabidiol plasma concentrations resulting in a decrease in efficacy. Cannabidiol is metabolized by CYP3A4; carbamazepine is a strong inducer of CYP3A4.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Carboplatin: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as carbamazepine, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear.
    Caspofungin: (Major) Data suggest that coadministration of inducers or mixed inducers/inhibitors of hepatic drug clearance along with caspofungin may result in reduced caspofungin blood concentrations. The reductions may be clinically significant. According to the manufacturer, drugs that may lead to reductions in caspofungin concentrations include carbamazepine. For adult patients receiving carbamazepine, an increase in the caspofungin dose to 70 mg/day should be considered. For pediatric patients receiving carbamazepine, a daily dosage of 70 mg/m2, not to exceed 70 mg, should be considered.
    Cefixime: (Moderate) Cefixime coadministered with carbamazepine has resulted in elevated carbamazepine concentrations according to postmarketing reports. Monitoring of carbamazepine plasma concentrations should be performed to detect any changes.
    Ceritinib: (Major) Avoid coadministration of ceritinib with carbamazepine due to decreased ceritinib exposure, resulting in decreased efficacy of treatment; carbamazepine exposure may also increase. Ceritinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of ceritinib by 70% and 44%, respectively. Additionally, ceritinib is a strong CYP3A4 inhibitor and carbamazepine is a CYP3A4 substrate with a narrow therapeutic index.
    Cerivastatin: (Minor) Significant CYP3A4 inducers, such as carbamazepine, may decrease the efficacy of HMG-CoA reductase inhibitors (Statins) which are CYP3A4 substrates, including cerivastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are coadministered.
    Cevimeline: (Minor) Inducers of cytochrome P450 3A4 or CYP 2D6 may cause a reduction in cevimeline plasma concentrations. Agents that potently induce CYP3A4 and/or CYP2D6 include carbamazepine.
    Charcoal: (Major) Note that charcoal exerts a nonspecific effect, and many medications can be adsorbed by activated charcoal. Use of activated charcoal as a dietary supplement for flatulence or other purposes is likely to decrease the effectiveness of agents like carbamazepine.
    Chlorambucil: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Chlordiazepoxide: (Moderate) Hepatic inducers, such as carbamazepine, can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chlordiazepoxide; Clidinium: (Moderate) Hepatic inducers, such as carbamazepine, can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Chloroquine: (Moderate) Chloroquine may antagonize the activity of carbamazepine. Dose adjustments of carbamazepine may be required if chloroquine is added or removed from an existing carbamazepine regimen.
    Chlorothiazide: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with carbamazepine 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 carbamazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Carbamazepine is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with carbamazepine 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 carbamazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Carbamazepine is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Chlorpromazine: (Moderate) The concomitant use of the phenothiazines and carbamazepine can increase CNS depression and reduce anticonvulsant effectiveness through a lowering of the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments. Carbamazepine is a potent inducer of the cytochrome P-450 hepatic oxidase system, and can reduce plasma concentrations of the phenothiazines. If a phenothiazine and carbamazepine must be used together, dosage adjustments of the phenothiazine may be required.
    Chlorthalidone: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Chlorthalidone; Clonidine: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Cimetidine: (Major) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as cimetidine, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely during coadministration; reduce carbamazepine doses may be necessary.
    Cinacalcet: (Moderate) Co-administration of cinacalcet with a CYP3A4 enzyme inducer may result in a decreased effect of cinacalcet. Agents that may significantly induce the CYP3A4 metabolism of cinacalcet include carbamazepine. Since these medications may increase the metabolism of cinacalcet, intact parathyroid hormone, serum calcium and serum phosphorous levels may need to be monitored.
    Ciprofloxacin: (Major) Serum carbamazepine concentrations should be monitored closely during coadministration with ciprofloxacin; reduced carbamazepine doses may be necessary. Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as ciprofloxacin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations.
    Cisapride: (Moderate) Cisapride is metabolized by the hepatic cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme. Inducers of CYP3A4, such as carbamazepine, may increase the clearance of cisapride.
    Cisatracurium: (Moderate) If neuromuscular blockers are administered to patients chronically receiving anticonvulsant agents such as carbamazepine, shorter durations of neuromuscular block may occur and infusion rates may be higher due to the development of resistance to muscle relaxants.
    Cisplatin: (Moderate) Cisplatin may increase the rate of carbamazepine metabolism via CYP3A4 induction. Monitor the serum carbamazepine concentration if cisplatin is used concurrently. The carbamazepine dose may need to be increased.
    Citalopram: (Moderate) Carbamazepine may potentially accelerate the hepatic metabolism of citalopram. Clinicians should be alert to altered effects of citalopram. Dosage adjustments may be necessary.
    Clarithromycin: (Major) Coadministration of carbamazepine 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. Additionally, carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as clarithromycin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely during coadministration; reduce carbamazepine doses may be necessary. Clarithromycin also inhibits epoxide hydrolase resulting in increased levels of the active metabolite carbamazepine 10, 11- epoxide, which may be more hepatotoxic than the parent drug. Several case reports have documented that clarithromycin can significantly decrease carbamazepine clearance, producing increases in the serum concentration of carbamazepine. Carbamazepine concentrations increased from 12 mcg/ml to 19.1 mcg/ml in a 17-year-old boy after 2 days of clarithromycin 250 mg PO bid. Patients should be monitored for carbamazepine toxicity if clarithromycin is added. Carbamazepine toxicity may be avoided if clarithromycin therapy is begun first and stabilized prior to beginning carbamazepine therapy, however, carbamazepine dosages may need to be increased if clarithromycin is subsequently discontinued.
    Clindamycin: (Moderate) Concomitant use of clindamycin and carbamazepine may increase clindamycin clearance and result in loss of efficacy of clindamycin. Clindamycin is a CYP3A4 substrate; carbamazepine is a strong inducer of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
    Clobazam: (Moderate) Carbamazepine induces CYP3A4 and clobazam is metabolized by CYP3A4; therefore, carbamazepine may potentially accelerate the hepatic metabolism of clobazam. Close monitoring of anticonvulsant efficacy and clinical effects is warranted.
    Clofazimine: (Moderate) Monitor for increased toxicity of carbamazepine if used concomitantly with clofazimine. Concomitant use may increase the concentration of carbamazepine, increasing the risk of adverse effects. Carbamazepine is a CYP3A4 substrate that has a narrow therapeutic index; in vitro data suggest clofazimine inhibits CYP3A4.
    Clonazepam: (Moderate) Monitoring of clonazepam concentrations or dosage adjustment may be necessary if used concurrently with carbamazepine due to decreased clonazepam concentrations. Clonazepam concentration decreases of approximately 38% have been reported when clonazepam is used with strong CYP3A4 inducers. Clonazepam is a CYP3A4 substrate. Carbamazepine is a strong CYP3A4 inducer. Additive CNS depression may also occur.
    Clorazepate: (Moderate) Carbamazepine is a hepatic inducers and can theoretically increase the clearance of clorazepate, leading to lower benzodiazepine concentrations.
    Clozapine: (Major) Coadministration of clozapine, a CYP3A4 substrate, with a potent inducer of CYP3A4, such as carbamazepine, is not recommended. If coadministration is necessary, monitor for decreased effectiveness of clozapine and consider increasing the clozapine dose if necessary. If the inducer is discontinued, reduce the clozapine dose based on clinical response. Carbamazepine may also increase the metabolism of clozapine through induction of CYP1A2. Both agents have myelosuppressive properties; patients should be monitored for and instructed about symptoms of infection. Lastly, close monitoring is recommended when clozapine is administered to patients with a seizure disorder because clozapine lowers the seizure threshold. The effectiveness of carbamazepine in treating seizures may be reduced. Dosage adjustments may be necessary and close monitoring is warranted when carbamazepine is used with clozapine.
    Cobicistat: (Severe) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy.
    Codeine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer. (Moderate) The concomitant use of the phenothiazines and carbamazepine can increase CNS depression and reduce anticonvulsant effectiveness through a lowering of the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments. Carbamazepine is a potent inducer of the cytochrome P-450 hepatic oxidase system, and can reduce plasma concentrations of the phenothiazines. If a phenothiazine and carbamazepine must be used together, dosage adjustments of the phenothiazine may be required.
    Codeine; Promethazine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer. (Moderate) The concomitant use of the phenothiazines and carbamazepine can increase CNS depression and reduce anticonvulsant effectiveness through a lowering of the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments. Carbamazepine is a potent inducer of the cytochrome P-450 hepatic oxidase system, and can reduce plasma concentrations of the phenothiazines. If a phenothiazine and carbamazepine must be used together, dosage adjustments of the phenothiazine may be required.
    Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of carbamazepine. To minimize potential for interactions, consider administering oral drugs with a narrow therapeutic index such as carbamazepine at least 1 hour before or at least 4 hours after colesevelam.
    Colestipol: (Major) Concurrent administration of carbamazepine with colestipol results in a modest reduction in carbamazepine bioavailability. Although the reduction in carbamazepine bioavailability may not be clinically significant, staggering the times of administration of these agents should alleviate any drug interaction. In the same study, cholestyramine did not affect carbamazepine bioavailability.
    Conivaptan: (Major) According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as carbamazepine, should be avoided. Coadministration of conivaptan with other CYP3A substrates (midazolam, simvastatin, amlodipine) has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with carbamazepine. Treatment with carbamazepine may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Conjugated Estrogens: (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Conjugated Estrogens; Bazedoxifene: (Moderate) Bazedoxifene undergoes metabolism by UGT enzymes in the intestinal tract and liver. The metabolism of bazedoxifene may be increased by concomitant use of substances known to induce UGTs, such as carbamazepine. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. In addition, in vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as carbamazepine, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Conjugated Estrogens; Medroxyprogesterone: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Copanlisib: (Major) Avoid the concomitant use of copanlisib and carbamazepine; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; carbamazepine is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
    Crizotinib: (Major) Avoid coadministration of crizotinib with carbamazepine due to decreased crizotinib exposure; increased carbamazepine exposure may also occur. Both drugs are CYP3A substrates. Crizotinib is also a moderate CYP3A inhibitor and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the AUC of crizotinib at steady-state by 84%.
    Cyclophosphamide: (Minor) Use caution if cyclophosphamide is used concomitantly with carbamazepine, and monitor for a possible increase in cyclophosphamide-related adverse events. The clinical significance of this interaction is unknown. Cyclophosphamide is a prodrug that is hydroxylated and activated primarily by CYP2B6; the contribution of CYP3A4 to the activation of cyclophosphamide is variable. N-dechloroethylation to therapeutically inactive but neurotoxic metabolites occurs primarily via CYP3A4. Additional isoenzymes involved in the activation of cyclophosphamide include CYP2A6, 2C9, and 2C19. The active metabolites, 4-hydroxycyclophosphamide and aldophosphamide, are inactivated by aldehyde dehydrogenase-mediated oxidation. Carbamazepine is a strong CYP3A4 inducer, as well as an inducer of CYP2A6, 2C9, and 2C19. It is not yet clear what effects CYP450 inducers have on the activation and/or toxicity of cyclophosphamide; the production of active or neurotoxic metabolites may be increased.
    Cyclosporine: (Moderate) Carbamazepine can increase the clearance of cyclosporine by inducing cyclosporine metabolism.
    Dabigatran: (Major) Avoid the concomitant administration of dabigatran and drugs that are strong inducers of P-gp, such as carbamazepine. Concomitant administration of dabigatran and carbamazepine results in decreased plasma concentrations of dabigatran that may be insufficient to achieve the intended therapeutic effect.
    Dabrafenib: (Major) Use dabrafenib and carbamazepine together with caution; concentrations of either agent may be decreased resulting in loss of efficacy. Use of an alternate agent in place of carbamazepine is recommended. If concomitant use cannot be avoided, monitor patients for loss of carbamazepine efficacy. Carbamazepine is a CYP3A4 substrate and a strong CYP3A4 inducer; dabrafenib is a CYP3A4 substrate and a moderate CYP3A4 inducer. The AUC values of dabrafenib and its metabolite desmethyl-dabrafenib were decreased by 34% and 30%, respectively, when dabrafenib was coadministered with another strong CYP3A4 inducer for 10 days in a drug interaction study.
    Daclatasvir: (Severe) Concomitant use of daclatasvir with carbamazepine is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Carbamazepine is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
    Dalfopristin; Quinupristin: (Moderate) Dalfopristin; quinupristin is a major inhibitor of cytochrome P450 3A4 and may decrease the elimination of drugs metabolized by this enzyme including carbamazepine.
    Danazol: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Danazol is known to inhibit CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations.
    Dapsone: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with carbamazepine is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and carbamazepine is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
    Darifenacin: (Minor) Carbamazepine may induce the CYP3A4 metabolism of darifenacin and thereby reduce its oral bioavailability. The dosage requirements of darifenacin may be increased in patients receiving concurrent enzyme inducers.
    Darolutamide: (Major) Avoid coadministration of darolutamide with carbamazepine due to the risk of decreased darolutamide plasma concentrations which may decrease efficacy. Carbamazepine is a P-glycoprotein (P-gp) inducer and a strong inducer of CYP3A4; darolutamide is a CYP3A4 substrate. Concomitant use with another combined P-gp and strong CYP3A4 inducer decreased the mean AUC and Cmax of darolutamide by 72% and 52%, respectively.
    Darunavir: (Major) Closely monitor for carbamazepine toxicity during coadministration; clinical monitoring of carbamazepine concentrations with dosage titration if necessary is also warranted. Coadministration of darunavir and carbamazepine may result in increased carbamazepine concentrations. In drug interaction studies, the concentration of darunavir was unaffected during coadministration with carbamazepine.
    Darunavir; Cobicistat: (Severe) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Closely monitor for carbamazepine toxicity during coadministration; clinical monitoring of carbamazepine concentrations with dosage titration if necessary is also warranted. Coadministration of darunavir and carbamazepine may result in increased carbamazepine concentrations. In drug interaction studies, the concentration of darunavir was unaffected during coadministration with carbamazepine.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Severe) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Administering tenofovir alafenamide with carbamazepine 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 (Major) Closely monitor for carbamazepine toxicity during coadministration; clinical monitoring of carbamazepine concentrations with dosage titration if necessary is also warranted. Coadministration of darunavir and carbamazepine may result in increased carbamazepine concentrations. In drug interaction studies, the concentration of darunavir was unaffected during coadministration with carbamazepine.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Severe) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir with carbamazepine is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to dasabuvir, ombitasvir, paritaprevir and ritonavir. Carbamazepine is a potent inducer and substrate of the hepatic isoenzyme CYP3A4; dasabuvir (minor), paritaprevir and ritonavir are substrates of this isoenzyme. In addition, carbamazepine induces P-glycoprotein (P-gp), a drug efflux transporter for which dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates. (Severe) Concomitant use of dasabuvir; ombitasvir; paritaprevir; ritonavir with carbamazepine is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to dasabuvir, ombitasvir, paritaprevir and ritonavir. Carbamazepine is a potent inducer and substrate of the hepatic isoenzyme CYP3A4; dasabuvir (minor), paritaprevir and ritonavir are substrates of this isoenzyme. In addition, carbamazepine induces P-glycoprotein (P-gp), a drug efflux transporter for which dasabuvir, ombitasvir, paritaprevir and ritonavir are substrates. (Major) Ritonavir decreases the hepatic CYP metabolism of carbamazepine, resulting in increased carbamazepine concentrations. In addition, carbamazepine increases the metabolism of the protease inhibitors and may lead to decreased efficacy of these medications. Carbamazepine is a potent inducer and substrate of the hepatic isoenzyme CYP3A4; ritonavir is a substrate and inhibitor of this isoenzyme. In addition, carbamazepine induces P-glycoprotein (P-gp), a drug efflux transporter for which ritonavir is a substrate. Treatment failures have been reported with protease inhibitors when carbamazepine is used concomitantly. The appropriate drug-dose adjustments necessary to ensure optimum levels of both antiretroviral drugs and carbamazepine are unknown. If used concomitantly, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or for carbamazepine toxicity.
    Dasatinib: (Major) Avoid coadministration of dasatinib and carbamazepine due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to carbamazepine with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Deflazacort: (Major) Avoid concomitant use of deflazacort and carbamazepine. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; carbamazepine is a strong inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
    Delavirdine: (Severe) Coadministration of carbamazepine and delavirdine is contraindicated due to the potential for loss of virologic response and possible resistance to delavirdine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Delavirdine may also increase plasma concentrations of carbamazepine. Delavirdine and carbamazepine are both substrates of CYP3A4; however, carbamazepine is a potent CYP3A4 inducer while delavirdine is a potent CYP3A4 inhibitor.
    Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including carbamazepine. The administration of carbamazepine prior to administration of desmopressin may act to reduce the duration of action of desmopressin. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
    Dexamethasone: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of dexamethasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with dexamethasone.
    Dexlansoprazole: (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Carbamazepine induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
    Dextroamphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    Dextromethorphan; Promethazine: (Moderate) The concomitant use of the phenothiazines and carbamazepine can increase CNS depression and reduce anticonvulsant effectiveness through a lowering of the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments. Carbamazepine is a potent inducer of the cytochrome P-450 hepatic oxidase system, and can reduce plasma concentrations of the phenothiazines. If a phenothiazine and carbamazepine must be used together, dosage adjustments of the phenothiazine may be required.
    Dextromethorphan; Quinidine: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Quinidine inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely if quinidine is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine in this situation.
    Diazepam: (Moderate) Carbamazepine is a potent inducer of the hepatic isoenzyme CYP3A4, one of the pathways responsible for the hepatic metabolism of diazepam. Monitor closely for signs of reduced diazepam effects.
    Diclofenac: (Moderate) Caution is advised when administering diclofenac with inducers of CYP2C9, such as carbamazepine. When used together, the systemic exposure to diclofenac (a CYP2C9 substrate) may decrease, potentially resulting in impaired efficacy. Higher diclofenac doses may be needed.
    Diclofenac; Misoprostol: (Moderate) Caution is advised when administering diclofenac with inducers of CYP2C9, such as carbamazepine. When used together, the systemic exposure to diclofenac (a CYP2C9 substrate) may decrease, potentially resulting in impaired efficacy. Higher diclofenac doses may be needed.
    Dienogest; Estradiol valerate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Diethylstilbestrol, DES: (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with carbamazepine 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 carbamazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Carbamazepine is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
    Diltiazem: (Major) Avoid coadministration of diltiazem and carbamazepine due to decreased plasma concentrations of diltiazem. Additionally, concomitant administration of diltiazem and carbamazepine has been reported to result in a 40% to 72% increase in carbamazepine plasma concentration resulting in toxicity in some cases. Monitor patients receiving these drugs concurrently for altered clinical response to therapy. Diltiazem is a CYP3A4 substrate and moderate inhibitor; carbamazepine is a CYP3A4 substrate and strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered diltiazem plasma concentrations to undetectable.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Disopyramide: (Moderate) Hepatic microsomal enzyme-inducing agents, such as carbamazepine, have the potential to accelerate the hepatic metabolism of disopyramide, a CYP3A4 substrate. Patients should be monitored for loss of disopyramide activity if carbamazepine is added. In addition, disopyramide doses may need to be reduced if acarbamazepine is stopped and disopyramide therapy is continued.
    Docetaxel: (Major) Avoid coadministration of docetaxel with carbamazepine due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Dolutegravir: (Major) When possible, avoid concurrent use of dolutegravir with carbamazepine in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive patients or treatment-experienced but INSTI-naive patients who weigh at least 40 kg, the dose of dolutegravir should be increased to 50 mg PO twice daily when administered with carbamazepine. For pediatric patients weighing 30 to 39 kg, the FDA-approved product labeling recommends increasing the dose of dolutegravir to 35 mg PO twice daily if administered concurrently with carbamazepine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Predictions regarding this interaction can be made based on the drugs metabolic pathways. Carbamazepine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Dolutegravir; Lamivudine: (Major) When possible, avoid concurrent use of dolutegravir with carbamazepine in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive patients or treatment-experienced but INSTI-naive patients who weigh at least 40 kg, the dose of dolutegravir should be increased to 50 mg PO twice daily when administered with carbamazepine. For pediatric patients weighing 30 to 39 kg, the FDA-approved product labeling recommends increasing the dose of dolutegravir to 35 mg PO twice daily if administered concurrently with carbamazepine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Predictions regarding this interaction can be made based on the drugs metabolic pathways. Carbamazepine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Dolutegravir; Rilpivirine: (Severe) Coadministration of carbamazepine and rilpivirine is contraindicated due to the potential for loss of virologic response and possible resistance to rilpivirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rilpivirine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. (Major) When possible, avoid concurrent use of dolutegravir with carbamazepine in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive patients or treatment-experienced but INSTI-naive patients who weigh at least 40 kg, the dose of dolutegravir should be increased to 50 mg PO twice daily when administered with carbamazepine. For pediatric patients weighing 30 to 39 kg, the FDA-approved product labeling recommends increasing the dose of dolutegravir to 35 mg PO twice daily if administered concurrently with carbamazepine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Predictions regarding this interaction can be made based on the drugs metabolic pathways. Carbamazepine is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Donepezil: (Moderate) The elimination of donepezil may be increased by concurrent administration of certain in vitro inducers of the hepatic isoenzymes CYP2D6 and/or CYP3A4, including carbamazepine.
    Donepezil; Memantine: (Moderate) The elimination of donepezil may be increased by concurrent administration of certain in vitro inducers of the hepatic isoenzymes CYP2D6 and/or CYP3A4, including carbamazepine.
    Doravirine: (Severe) Coadministration of carbamazepine and doravirine is contraindicated due to the potential for loss of virologic response and possible resistance to doravirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). If doravirine use is necessary, discontinue carbamazepine at least 4-weeks prior to initiation. Doravirine is a CYP3A4 substrate and carbamazepine is a potent CYP3A4 inducer.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Severe) Coadministration of carbamazepine and doravirine is contraindicated due to the potential for loss of virologic response and possible resistance to doravirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). If doravirine use is necessary, discontinue carbamazepine at least 4-weeks prior to initiation. Doravirine is a CYP3A4 substrate and carbamazepine is a potent CYP3A4 inducer.
    Doxacurium: (Moderate) If neuromuscular blockers are administered to patients chronically receiving anticonvulsant agents such as carbamazepine, shorter durations of neuromuscular block may occur and infusion rates may be higher due to the development of resistance to muscle relaxants.
    Doxercalciferol: (Moderate) Hepatic enzyme inducers such as carbamazepine, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Doxorubicin: (Major) As carbamazepine is metabolized by CYP3A4, the potential exists for an interaction between carbamazepine and doxorubicin HCl, which isexpected to decrease plasma concentrations of carbamazepine. A 36-year old female with a seizure disorder and cancer had a seizure due to subtherapeutic carbamazepine, phenytoin, and valproate concentrations after 2 days of doxorubicin and cisplatin receipt. The exact mechanism of the interaction is unknown, but decreased absorption or accelerated elimination of carbamazepine may be the cause. Additionally, carbamazepine is a potent inducer of CYP3A4 and P-glycoprotein (P-gp); doxorubicin is a major substrate of both CYP3A4 and P-gp. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of carbamazepine and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy; additionally, closely monitor the serum carbamazepine concentration, as the dose may need to be increased.
    Doxycycline: (Major) Carbamazepine may potentially accelerate the hepatic metabolism of doxycycline. Clinicians should be alert to decreased effect of doxycycline. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with doxycycline.
    Dronabinol: (Major) Use caution if coadministration of dronabinol with carbamazepine is necessary, and monitor for a decrease in the efficacy of dronabinol; also monitor for an increase in carbamazepine-related adverse effects. Dronabinol is a CYP2C9 and 3A4 substrate; carbamazepine is a strong inducer of CYP2C9 and 3A4. Concomitant use may result in decreased plasma concentrations of dronabinol. Additionally, dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
    Dronedarone: (Major) The concomitant use of dronedarone and CYP3A4 inducers should be avoided. Dronedarone is metabolized by CYP3A. Carbamazepine induces CYP3A4. Coadministration of CYP3A4 inducers, such as carbamazepine, with dronedarone may result in reduced plasma concentration and subsequent reduced effectiveness of dronedarone therapy.
    Drospirenone: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin.
    Drospirenone; Estradiol: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Drospirenone; Ethinyl Estradiol: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus. (Moderate) High doses of folate may cause decreased serum concentrations of carbamazepine resulting in a decrease in effectiveness and, possibly, an increase in the frequency of seizures in susceptible patients. In addition, L-methylfolate plasma levels may be decreased when administered with carbamazepine. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents and patients should be monitored closely for seizure activity.
    Dupilumab: (Moderate) Coadministration of dupilumab may result in altered exposure to carbamazepine. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP450 enzymes could be normalized during dupilumab administration. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as carbamazepine. Monitor carbamazepine concentrations if dupilumab is initiated or discontinued in a patient taking carbamazepine; carbamazepine dose adjustments may be needed.
    Duvelisib: (Major) Avoid coadministration of duvelisib with carbamazepine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; carbamazepine is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
    Edoxaban: (Major) Avoid the concomitant administration of edoxaban and carbamazepine. Concomitant administration of edoxaban and carbamazepine results in decreased plasma concentrations of edoxaban that may be insufficient to achieve the intended therapeutic effect.
    Efavirenz: (Major) Coadministration of carbamazepine and efavirenz is not recommended due to the potential for loss of virologic response and possible resistance to efavirenz or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Efavirenz may also decrease plasma concentrations of carbamazepine. Monitor carbamazepine and efavirenz concentration, or if possible, use an alternative anticonvulsant. In drug interaction studies, coadministration of carbamazepine and efavirenz resulted in a 27% decrease in carbamazepine AUC and a 36% decrease in the efavirenz AUC.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of carbamazepine and efavirenz is not recommended due to the potential for loss of virologic response and possible resistance to efavirenz or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Efavirenz may also decrease plasma concentrations of carbamazepine. Monitor carbamazepine and efavirenz concentration, or if possible, use an alternative anticonvulsant. In drug interaction studies, coadministration of carbamazepine and efavirenz resulted in a 27% decrease in carbamazepine AUC and a 36% decrease in the efavirenz AUC.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of carbamazepine and efavirenz is not recommended due to the potential for loss of virologic response and possible resistance to efavirenz or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Efavirenz may also decrease plasma concentrations of carbamazepine. Monitor carbamazepine and efavirenz concentration, or if possible, use an alternative anticonvulsant. In drug interaction studies, coadministration of carbamazepine and efavirenz resulted in a 27% decrease in carbamazepine AUC and a 36% decrease in the efavirenz AUC.
    Elagolix: (Moderate) Concomitant use of elagolix and carbamazepine may result in decreased concentrations of elagolix and/or carbamazepine; monitor for decreased efficacy of both drugs with coadministration. Elagolix is a CYP3A substrate and a weak to moderate inducer; carbamazepine is a strong inducer and substrate of CYP3A4.
    Elbasvir; Grazoprevir: (Severe) Concurrent administration of elbasvir; grazoprevir with carbamazepine is contraindicated. Carbamazepine is a strong CYP3A inducer, while both elbasvir and grazoprevir are substrates of CYP3A. Use of these drugs together is expected to significantly decrease the plasma concentrations of both elbasvir and grazoprevir, and may result in decreased virologic response.
    Elexacaftor; tezacaftor; ivacaftor: (Major) Coadministration of elexacaftor; tezacaftor; ivacaftor with carbamazepine is not recommended as concurrent use may decrease exposure of elexacaftor; tezacaftor; ivacaftor. Elexacaftor, tezacaftor, and ivacaftor are CYP3A4 substrates (ivacaftor is a sensitive CYP3A4 substrate). Carbamazepine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer significantly decreased ivacaftor exposure by 89%; elexacaftor and tezacaftor exposures are expected to also decrease during coadministration of strong CYP3A4 inducers. (Major) Coadministration of ivacaftor with carbamazepine is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Do not administer tezacaftor; ivacaftor and carbamazepine together; coadministration may reduce the efficacy of tezacaftor; ivacaftor. Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by the concomitant use of carbamazepine, a strong CYP3A inducer; both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate). Coadministration of ivacaftor with a strong CYP3A inducer decreased ivacaftor exposure 89%.
    Eliglustat: (Major) Coadministration of eliglustat and carbamazepine significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. Carbamazepine is a strong CYP3A inducer, and eliglustat is a CYP3A substrate.
    Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as carbamazepine, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
    Elvitegravir: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Carbamazepine 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 carbamazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Severe) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Administering tenofovir alafenamide with carbamazepine 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 (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. Carbamazepine 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 carbamazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Severe) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy. (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. Carbamazepine 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 carbamazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
    Emapalumab: (Moderate) Monitor for decreased efficacy of carbamazepine and adjust the dose as needed during coadministration with emapalumab. Carbamazepine is a CYP3A4, CYP1A2, and CYP2C8 substrate with a narrow therapeutic index. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism.
    Empagliflozin; Linagliptin: (Major) Carbamazepine is an inducer of CYP3A4 and p-glycoprotein; oxcarbazepine is an inducer of CYP3A4. Inducers of CYP3A4 or p-glycoprotein can decrease exposure to linagliptin to subtherapeutic and likely ineffective concentrations. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Severe) Coadministration of carbamazepine and rilpivirine is contraindicated due to the potential for loss of virologic response and possible resistance to rilpivirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rilpivirine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. (Major) Administering tenofovir alafenamide with carbamazepine 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
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Severe) Coadministration of carbamazepine and rilpivirine is contraindicated due to the potential for loss of virologic response and possible resistance to rilpivirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rilpivirine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Emtricitabine; Tenofovir alafenamide: (Major) Administering tenofovir alafenamide with carbamazepine 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
    Enalapril; Felodipine: (Moderate) Carbamazepine induces CYP3A4 and may significantly enhance the hepatic metabolism of felodipine. Higher doses of felodipine may be necessary in epileptic patients receiving carbamazepine.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Encorafenib: (Major) Avoid coadministration of encorafenib and carbamazepine due to decreased encorafenib exposure and potential loss of efficacy. Encorafenib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration with CYP3A4 inducers has not been studied with encorafenib; however, in clinical trials, steady-state encorafenib exposures were lower than encorafenib exposures after the first dose, suggesting CYP3A4 auto-induction.
    Enflurane: (Moderate) Caution is advised with the concomitant use of enflurane and carbamazepine as concurrent use may increase the risk of hepatotoxicity.
    Enteral Feedings: (Moderate) Concurrent enteral feedings appear to slow or impede the absorption of carbamazepine suspension from the GI tract. Where possible, hold continuous enteral feedings at least 15 minutes before and 15 minutes after the administration of a carbamazepine suspension dose. Flush enteral tubes with appropriate volumes of water or other compatible fluid before and after carbamazepine suspension administration.
    Entrectinib: (Major) Avoid coadministration of entrectinib with carbamazepine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
    Enzalutamide: (Major) Avoid coadministration of carbamazepine with enzalutamide if possible due to decreased enzalutamide exposure which may compromise efficacy; carbamazepine plasma concentrations may also decrease. If concomitant use is unavoidable, increase the dose of enzalutamide from 160 mg to 240 mg once daily; the original dose of enzalutamide may be resumed when carbamazepine is discontinued. An increased dose of carbamazepine may also be necessary; monitor carbamazepine concentrations. Both enzalutamide and carbamazepine are substrates and strong inducers of CYP3A4. The composite AUC of enzalutamide plus N-desmethyl enzalutamide decreased by 37% in the presence of a strong CYP3A4 inducer. CYP3A4 inducers can decrease serum concentrations of carbamazepine and decrease its effectiveness.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Eravacycline: (Major) Increase the dose of eravacycline to 1.5 mg/kg IV every 12 hours when coadministered with a strong CYP3A4 inducer, such as carbamazepine. Concomitant use of strong CYP3A4 inducers decreases the exposure of eravacycline, which may reduce its efficacy. When eravacycline was administered with a strong CYP3A4/3A5 inducer, the eravacycline AUC was decreased by 35% and its clearance was increased by 54%.
    Erdafitinib: (Major) Avoid coadministration of erdafitinib and carbamazepine due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate; carbamazepine is a strong CYP3A4 inducer as well as a CYP2C9 inducer.
    Erlotinib: (Major) Avoid coadministration of erlotinib with carbamazepine if possible due to the risk of decreased erlotinib efficacy. If concomitant use is unavoidable, increase the dose of erlotinib in 50 mg increments at 2-week intervals as tolerated (maximum dose, 450 mg). Erlotinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2. Carbamazepine is a strong CYP3A4 inducer as well as a CYP1A2 inducer. Coadministration with another strong CYP3A4 inducer decreased erlotinib exposure by 58% to 80%.
    Erythromycin: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Erythromycin inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations.
    Erythromycin; Sulfisoxazole: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Erythromycin inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations.
    Escitalopram: (Moderate) Monitor for altered clinical effect of escitalopram when carbamazepine is coadministered. CYP3A4 and CYP2C19 are the primary isoenzymes involved in the metabolism of escitalopram and carbamazepine is a potent CYP3A4 inducer. Coadministration of citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine. Although trough citalopram plasma levels were unaffected, carbamazepine may increase the clearance of escitalopram. Additive CNS effects, such as sedation, may also be possible.
    Eslicarbazepine: (Major) Because carbamazepine and eslicarbazepine are chemically related, coadministration may result in an increased incidence of adverse reactions. In addition, carbamazepine reduces the plasma concentration of eslicarbazepine. Dosage adjustment of eslicarbazepine and carbamazepine may be necessary based on efficacy and tolerability.
    Esomeprazole: (Moderate) Coadministration may result in increased carbamazepine serum concentrations and decreased esomeprazole serum concentrations. Carbamazepine induces cytochrome P-450 enzymes, including those responsible for the metabolism of esomeprazole possibly resulting in reduced esomeprazole concentrations. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy. In addition, in one study, multiple dose administration of another PPI, omeprazole, increased the Cmax, AUC, and elimination half-life of carbamazepine when given as an extended-release formulation in healthy male volunteers. Based on these results, it would be prudent to monitor carbamazepine serum concentrations when esomeprazole is added to the drug regimen.
    Esomeprazole; Naproxen: (Moderate) Coadministration may result in increased carbamazepine serum concentrations and decreased esomeprazole serum concentrations. Carbamazepine induces cytochrome P-450 enzymes, including those responsible for the metabolism of esomeprazole possibly resulting in reduced esomeprazole concentrations. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy. In addition, in one study, multiple dose administration of another PPI, omeprazole, increased the Cmax, AUC, and elimination half-life of carbamazepine when given as an extended-release formulation in healthy male volunteers. Based on these results, it would be prudent to monitor carbamazepine serum concentrations when esomeprazole is added to the drug regimen.
    Estazolam: (Moderate) Carbamazepine is a hepatic inducer and can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, possibly leading to reduced benzodiazepine concentrations.
    Esterified Estrogens: (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Esterified Estrogens; Methyltestosterone: (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Estradiol Cypionate; Medroxyprogesterone: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Estradiol: (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Estradiol; Levonorgestrel: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Estradiol; Norethindrone: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Estradiol; Norgestimate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Estradiol; Progesterone: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Estramustine: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Estrogens: (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Estropipate: (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Eszopiclone: (Moderate) Potent inducers of CYP3A4, such as carbamazepine, may increase the rate of eszopiclone metabolism, resulting in decreased systemic eszopiclone concentrations.
    Ethanol: (Moderate) Because of its primary CNS effect, caution should be used when carbamazepine is taken with other centrally acting drugs such as ethanol. The limited evidence from pharmacokinetic studies suggests that neither acute nor chronic ethanol use will significantly alter the pharmacokinetics of carbamazepine.
    Ethinyl Estradiol: (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Desogestrel: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Etonogestrel: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Levonorgestrel: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus. (Moderate) High doses of folate may cause decreased serum concentrations of carbamazepine resulting in a decrease in effectiveness and, possibly, an increase in the frequency of seizures in susceptible patients. In addition, L-methylfolate plasma levels may be decreased when administered with carbamazepine. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents and patients should be monitored closely for seizure activity.
    Ethinyl Estradiol; Norelgestromin: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Norethindrone Acetate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Norethindrone: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Norgestimate: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethinyl Estradiol; Norgestrel: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin. (Moderate) Concurrent administration of estrogens with carbamazepine may reduce plasma estrogen concentrations and therefore reduce the clinical efficacy of estrogen products. If an estrogen-containing product is being used for contraception, consider an alternate or additional form of contraception; unintended pregnancy has occurred in women who relied on hormonal contraceptives and received carbamazepine. The alternative contraceptive agent may need to be continued for 1 month after discontinuation of carbamazepine. Women taking estrogen for hormone replacement may require a dosage adjustment. Women taking estrogen products for any indication and carbamazepine should report breakthrough bleeding to their prescriber. Estrogens are metabolized by CYP3A4, and carbamazepine is a potent CYP3A4 inducer. Additionally, patients taking both anticonvulsants and estrogen may be at higher risk of folate deficiency secondary to additive effects on folate metabolism. If contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in the fetus.
    Ethosuximide: (Moderate) Carbamazepine induces hepatic microsomal enzymes. Increased hepatic metabolism of ethosuximide leads to a decrease in its plasma concentration and a reduction in its half-life. To maintain a therapeutic dosage, serum concentrations of ethosuximide should be measured, especially if additional anticonvulsant therapy is added to or withdrawn from ethosuximide therapy.
    Ethotoin: (Moderate) Carbamazepine induces hepatic microsomal enzymes, which, in turn, accelerates carbamazepine metabolism or the metabolism of other drugs. Interactions between carbamazepine and other anticonvulsants, such as the hydantoins, are complex. Despite the fact that one anticonvulsant may interact with another, combinations of anticonvulsants are frequently used in patients who are refractory to one agent alone and may change the profile of expected drug interactions. Phenytoin or fosphenytoin (and possibly ethotoin) can potentially be affected by carbamazepine enzyme induction. Phenytoin plasma concentrations have also been reported to increase and decrease in the presence of carbamazepine. As carbamazepine is metabolized by CYP3A4, the potential exists for an interaction between carbamazepine and hydantoins, which induce CYP3A4 and therefore may decrease plasma concentrations of carbamazepine. Careful monitoring of carbamazepine and hydantoin plasma concentrations, along with close clinical monitoring of response to therapy, is advised.
    Etonogestrel: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin.
    Etoposide, VP-16: (Major) Monitor for clinical efficacy of etoposide, VP-16 when coadministered with carbamazepine, as concomitant use is associated with increased etoposide clearance and reduced efficacy. Carbamazepine is a strong inducer of CYP3A4; etoposide, VP-16 is a CYP3A4 substrate. In addition, myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution.
    Etravirine: (Major) Coadministration of carbamazepine and etravirine is not recommended due to the potential for loss of virologic response and possible resistance to etravirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Etravirine may also alter plasma concentrations of carbamazepine. Consider alternative anticonvulsant treatment. Etravirine is a substrate of CYP3A4, CYP2C9, and CYP2C19; it also induces CYP3A4. Carbamazepine is a CYP3A4 substrate and an inducer of CYP3A4 (strong), CYP2C9, and CYP2C19.
    Everolimus: (Major) Depending on the indication, coadministration of carbamazepine with everolimus may need to be avoided or an everolimus dose adjustment may be necessary due to decreased plasma concentrations of everolimus. For patients with breast cancer, neuroendocrine tumors, renal cell carcinoma, and renal angiolipoma with tubular sclerosis complex (TSC), avoid concomitant use where alternatives exist. If concurrent use cannot be avoided, double the daily dose of everolimus using increments of 5 mg or less. Resume the previous dose after the inducer has been discontinued for 5 days. For patients with subependymal giant cell astrocytoma (SEGA) with TSC or TSC-associated partial-onset seizures, double the daily dose of everolimus using increments of 5 mg or less; multiple increments may be required. Addition of a second strong CYP3A4 inducer may not require additional dosage modifications. Assess trough concentrations when initiating and discontinuing the inducer. Subsequent dosing should be guided by therapeutic drug monitoring. Resume the previous dose of everolimus once all inducers are discontinued for 5 days. Coadministration of carbamazepine with everolimus (Zortress) is not recommended without close monitoring of everolimus whole blood trough concentrations. Everolimus is a CYP3A4 substrate as well as a substrate of P-glycoprotein (P-gp); carbamazepine is a strong inducer of CYP3A4 and a P-gp inducer. Coadministration with another strong CYP3A4/P-gp inducer decreased everolimus exposure by 63%.
    Exemestane: (Major) If coadministration of exemestane with carbamazepine is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
    Ezetimibe; Simvastatin: (Minor) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, including simvastatin.
    Ezogabine: (Major) During concurrent use of ezogabine 300-1200 mg/day and carbamazepine 600-2400 mg/day, the AUC and Cmax of ezogabine were reduced by 31% and 23%, respectively. An increase in the dose of ezogabine should be considered during concurrent use of carbamazepine.
    Fedratinib: (Major) Avoid coadministration of fedratinib with carbamazepine as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. The coadministration of fedratinib with a strong CYP3A4 inducer has not been evaluated.
    Felbamate: (Moderate) Concurrent administration of felbamate and other antiepileptic drugs results in changes in serum concentrations of both felbamate and the antiepileptic drugs. Felbamate causes a decrease in the steady-state plasma concentration of carbamazepine but increases concentrations of carbamazepine epoxide, a carbamazepine metabolite.
    Felodipine: (Moderate) Carbamazepine induces CYP3A4 and may significantly enhance the hepatic metabolism of felodipine. Higher doses of felodipine may be necessary in epileptic patients receiving carbamazepine.
    Fentanyl: (Moderate) Monitor for reduced efficacy of fentanyl and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of fentanyl as needed. If carbamazepine is discontinued, consider a dose reduction of fentanyl and frequently monitor for signs or respiratory depression and sedation. Fentanyl is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease fentanyl levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    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 carbamazepine, a strong CYP3A4 inducer, is not recommended.
    Fluconazole: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Fluconazole inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations.
    Flucytosine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants, including carbamazepine.
    Fluoxetine: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Fluoxetine inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations.
    Fluoxetine; Olanzapine: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Fluoxetine inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. (Moderate) Monitor for reduced olanzapine efficacy; dosage adjustments might be necessary in some patients. Carbamazepine increases olanzapine clearance by approximately 50% via potent induction of CYP1A2. The clearance of olanzapine may be increased with higher doses of carbamazepine. In addition, additive CNS effects (e.g., sedation) may occur, and antipsychotic therapy may also reduce the seizure threshold in some patients.
    Fluphenazine: (Moderate) The concomitant use of the phenothiazines and carbamazepine can increase CNS depression and reduce anticonvulsant effectiveness through a lowering of the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments. Carbamazepine is a potent inducer of the cytochrome P-450 hepatic oxidase system, and can reduce plasma concentrations of the phenothiazines. If a phenothiazine and carbamazepine must be used together, dosage adjustments of the phenothiazine may be required.
    Flurazepam: (Moderate) Carbamazepine is a hepatic inducer and can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
    Fluticasone: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
    Fluticasone; Salmeterol: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
    Fluticasone; Vilanterol: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
    Fluvoxamine: (Moderate) Carbamazepine is metabolized by CYP3A4 and fluvoxamine is known to inhibit this enzyme. Serum carbamazepine concentrations should be monitored closely if fluvoxamine is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine in this situation. At least one case is noted where carbamazepine serum concentrations increased substantially when fluvoxamine was added, accompanied by signs of carbamazepine toxicity.
    Folate analogs: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Fomepizole: (Minor) Carbabamezapine may decrease the actions of Fomepizole via induction of the CYP450 hepatic enzyme system. This interaction has not been studied, and its clinical significance has not been established.
    Food: (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with carbamazepine. Carbamazepine is an inducer of CYP2C9 and CYP3A4, two isoenzymes responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with carbamazepine, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be increased. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Fosamprenavir: (Moderate) Monitor for decreased efficacy of fosamprenavir during coadministration of carbamazepine. Additionally, monitor carbamazepine concentrations closely as increased side effects may occur; dose adjustments may be needed. Coadministration may result in decreased concentrations of the active metabolite of fosamprenavir, amprenavir, and increased carbamazepine concentrations. Carbamazepine is a substrate and potent inducer of CYP3A; fosamprenavir is a substrate and potent inhibitor of CYP3A4.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Fosphenytoin: (Moderate) Carbamazepine induces hepatic microsomal enzymes, which, in turn, accelerates carbamazepine metabolism or the metabolism of other drugs. Interactions between carbamazepine and other anticonvulsants, such as the hydantoins, are complex. Despite the fact that one anticonvulsant may interact with another, combinations of anticonvulsants are frequently used in patients who are refractory to one agent alone and may change the profile of expected drug interactions. Phenytoin or fosphenytoin (and possibly ethotoin) can potentially be affected by carbamazepine enzyme induction. Phenytoin plasma concentrations have also been reported to increase and decrease in the presence of carbamazepine. As carbamazepine is metabolized by CYP3A4, the potential exists for an interaction between carbamazepine and hydantoins, which induce CYP3A4 and therefore may decrease plasma concentrations of carbamazepine. Careful monitoring of carbamazepine and hydantoin plasma concentrations, along with close clinical monitoring of response to therapy, is advised.
    Fostamatinib: (Major) Avoid the concomitant use of fostamatinib with carbamazepine. Concomitant use of fostamatinib with a strong CYP3A4 inducer decreases exposure to the major active metabolite, R406. R406 is extensively metabolized by CYP3A4; carbamazepine is a strong CYP3A4 inducer. Concomitant use of fostamatinib with another strong CYP3A4 inducer decreased R406 AUC by 75% and Cmax by 59%.
    Galantamine: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of CYP3A4 inducers such as carbamazepine.
    Gefitinib: (Major) Increase the dose of gefitinib to 500 mg PO once daily if coadministration with carbamazepine is necessary. If carbamazepine is discontinued, gefitinib at a dose of 250 mg once daily may be resumed 7 days later. Gefitinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer reduced gefitinib exposure by 83%.
    Gemfibrozil: (Moderate) Use carbamazepine and gemfibrozil together with caution. Carbamazepine is a substrate of CYP2C8, and gemfibrozil is a strong CYP2C8 inhibitor. Coadministration may result in a significant increase in carbamazepine exposure. A dose reduction of carbamazepine may be required if used concomitantly with gemfibrozil.
    Gilteritinib: (Major) Avoid coadministration of gilteritinib and carbamazepine due to the potential for decreased gilteritinib exposure and risk of decreased efficacy. Gilteritinib is a P-gp and CYP3A4 substrate; carbamazepine is a combined P-gp and strong CYP3A4 inducer. Coadministration of another combined P-gp and strong CYP3A4 inducer decreased the gilteritinib AUC by 70% in a drug interaction study.
    Givosiran: (Major) Avoid concomitant use of givosiran and carbamazepine due to the risk of increased carbamazepine-related adverse reactions. If use is necessary, consider reducing the carbamazepine dose. Carbamazepine is a CYP1A2 substrate. Givosiran may moderately reduce hepatic CYP1A2 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
    Glasdegib: (Major) Avoid coadministration of glasdegib and carbamazepine due to the potential for decreased glasdegib exposure and risk of decreased efficacy. Glasdegib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the glasdegib AUC by 70% in a drug interaction study.
    Glecaprevir; Pibrentasvir: (Major) Coadministration of glecaprevir with carbamazepine is not recommended due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); carbamazepine is a CYP3A4/P-gp inducer. In drug interaction studies, coadministration of carbamazepine with glecaprevir resulted in a 66% decrease in the AUC of glecaprevir. (Major) Coadministration of pibrentasvir with carbamazepine is not recommended due to the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); carbamazepine is an inducer of P-gp. Coadministration may decrease plasma concentrations of pibrentasvir. In drug interaction studies, coadministration of carbamazepine with pibrentasvir resulted in a 51% decrease in the AUC of pibrentasvir.
    Glimepiride: (Minor) Carbamazepine may induce the CYP2C9 metabolism of glimepiride. Blood glucose concentrations should be monitored and possible dose adjustments of glimepiride may need to be made.
    Glimepiride; Pioglitazone: (Minor) Carbamazepine may induce the CYP2C9 metabolism of glimepiride. Blood glucose concentrations should be monitored and possible dose adjustments of glimepiride may need to be made.
    Glimepiride; Rosiglitazone: (Minor) Carbamazepine may induce the CYP2C9 metabolism of glimepiride. Blood glucose concentrations should be monitored and possible dose adjustments of glimepiride may need to be made.
    Glycerol Phenylbutyrate: (Moderate) Concomitant use of glycerol phenylbutyrate and carbamazepine may result in decreased exposure of carbamazepine. Carbamazepine is a CYP3A substrate; glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of carbamazepine during coadministration.
    Grapefruit juice: (Moderate) Grapefruit juice has been shown to increase carbamazepine peak and trough serum concentrations and the AUC by up to 40 percent. Grapefruit juice contains a compound that inhibits CYP3A4 in enterocytes. Increased sedation or other side effects may be possible. It is recommended that patients not significantly alter their grapefruit ingestion while taking carbamazepine.
    Green Tea: (Minor) Some, but not all, green tea products contain caffeine. Medications that may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme include carbamazepine.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Guanfacine: (Major) Carbamazepine can significantly decrease guanfacine plasma concentrations; guanfacine dosage adjustment is recommended. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, doubling the recommended dose of guanfacine should be considered. If carbamazepine is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If carbamazepine is discontinued, decrease the guanfacine ER dosage back to the recommended dose over 1 to 2 weeks. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is primarily metabolized by CYP3A4, and carbamazepine is a strong CYP3A4 inducer.
    Guanidine: (Minor) Bone marrow suppression is associated with guanidine therapy. Avoid concomitant use of other drugs known to cause bone marrow suppression such as carbamazepine.
    Haloperidol: (Major) Carbamazepine may potentially accelerate the hepatic metabolism of haloperidol. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with haloperidol.
    Halothane: (Moderate) Caution is advised with the concomitant use of halothane and carbamazepine as concurrent use may increase the risk of hepatotoxicity.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Hydantoins: (Moderate) Carbamazepine induces hepatic microsomal enzymes, which, in turn, accelerates carbamazepine metabolism or the metabolism of other drugs. Interactions between carbamazepine and other anticonvulsants, such as the hydantoins, are complex. Despite the fact that one anticonvulsant may interact with another, combinations of anticonvulsants are frequently used in patients who are refractory to one agent alone and may change the profile of expected drug interactions. Phenytoin or fosphenytoin (and possibly ethotoin) can potentially be affected by carbamazepine enzyme induction. Phenytoin plasma concentrations have also been reported to increase and decrease in the presence of carbamazepine. As carbamazepine is metabolized by CYP3A4, the potential exists for an interaction between carbamazepine and hydantoins, which induce CYP3A4 and therefore may decrease plasma concentrations of carbamazepine. Careful monitoring of carbamazepine and hydantoin plasma concentrations, along with close clinical monitoring of response to therapy, is advised.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as carbamazepine. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Hydroxyprogesterone: (Major) Concomitant use of carbamazepine with hormonal products may render the hormonal product less effective. The plasma concentrations of the hormones may be decreased because carbamazepine induces the activity of hepatic metabolic enzymes. 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 progestins for other indications may need to be monitored for reductions in clinical effect of the progestin.
    Ibrutinib: (Major) Avoid the concomitant use of ibrutinib and carbamazepine; ibrutinib plasma concentrations may decrease. Ibrutinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ibrutinib exposure by more than 10-fold.
    Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of oxycodone as needed. If carbamazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
    Idelalisib: (Severe) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a