Antiepileptics. Carboxamide derivatives
ATC code: N03AF01 (Carbamazepine)
Brand names
Tegretol, Tegretol XR, Carbatrol, Epitol, Equetro
Blocks voltage-gated sodium channels, stabilizes neuronal membranes. Used for partial epilepsy, trigeminal neuralgia, mood stabilization in bipolar disorder. Potent CYP3A4, CYP2C9, P-gp inducer. HLA-B*15:02 screening in Asian-origin patients before starting therapy to exclude SJS/TEN risk.
First line
Carbamazepine and oxcarbazepine are first-line drugs for focal epilepsy in adults and children. NG217 2022 recommends carbamazepine or lamotrigine as first choice for focal seizures. ILAE and Russian clinical guidelines align with this. The drug reduces seizure frequency by more than 50% in 60–70% of patients with focal epilepsy.
In patients of Asian descent (Han Chinese, Thai, Indonesian), HLA-B*15:02 genotyping is recommended before initiation due to high risk of severe cutaneous reactions.
Sources
First line
Carbamazepine remains the first-line drug for trigeminal neuralgia per 2017 and European guidelines. NNT for 50% pain reduction is approximately 1.7. Starting dose 100–200 mg twice daily, titrated to clinical response (usually 600–1200 mg/day). Oxcarbazepine is considered an alternative with better tolerability.
When pharmacotherapy fails and pain is disabling, consider microvascular decompression or gamma knife radiosurgery.
Second line
Carbamazepine is considered an alternative to benzodiazepines for mild-to-moderate alcohol withdrawal in outpatients without seizure risk. Meta-analyses show comparable efficacy in this subgroup. For severe withdrawal and delirium risk, benzodiazepines remain first-line.
Third line
In bipolar disorder, carbamazepine is used as a third-line mood stabilizer after lithium and valproate. CG185 and RANZCP 2022 recommend considering carbamazepine when first-line drugs are intolerable or ineffective. Effective for acute mania and maintenance therapy. Use is complicated by strong CYP induction and drug interaction risk.
In Russia, the bipolar disorder indication is registered only for selected brand names (e.g., Zeptol); use is off-label per clinical guidelines.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Carbamazepine is an antiepileptic drug. It is prescribed for epilepsy, trigeminal neuralgia, and bipolar disorder ( 2018 and NG137 guidelines). For everyday mood stabilization, carbamazepine does not work: no clinical studies of such use exist. The drug carries serious risks: severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) in HLA-B*1502 carriers, aplastic anemia, agranulocytosis ( boxed warning). Carbamazepine also strongly accelerates metabolism of many other drugs (CYP3A4 inducer), sharply reducing their effectiveness. If carbamazepine was prescribed for mood stabilization, consider seeking a second opinion.
Carbamazepine reduces erythrocyte folate level with long-term therapy. In women of reproductive age planning pregnancy, folic acid 4–5 mg/day is recommended for 1–3 months preconception and during the first trimester to reduce neural tube defect risk.
Source: FDA: Tegretol (carbamazepine) prescribing information (2018)
Carbamazepine induces CYP24A1 and accelerates 25(OH) vitamin D catabolism. Long-term therapy (over 2 years) is associated with reduced 25(OH) vitamin D level and osteopenia. Check level annually and supplement cholecalciferol 800–2000 IU/day when level falls to 30 ng/mL or below.
Source: FDA: Tegretol (carbamazepine) prescribing information (2018)
Long-term carbamazepine use is associated with decreased serum biotin in some patients. Clinical deficiency manifestations (seborrheic dermatitis, hair loss) are rare and usually require dietary correction rather than routine supplementation.
Source: FDA: Tegretol (carbamazepine) prescribing information (2018)
24 pairs found. Sorted from critical to minor.
Mechanism
Carbamazepine is a strong CYP3A4 inducer. It accelerates dronedarone clearance: levels drop by 80% and antiarrhythmic effect is lost. Multaq Section 4.3 specifically lists strong CYP3A4 inducers (rifampicin, carbamazepine, phenobarbital).
Symptoms
First, recurrence of atrial fibrillation symptoms: palpitations, irregular pulse, fatigue, dyspnoea. Possible rhythm breakthroughs requiring admission.
Management
The combination is not prescribed. During carbamazepine therapy, switch to amiodarone (less affected by CYP3A4 induction) or rhythm control via catheter ablation. Alternative anticonvulsants: levetiracetam, lamotrigine (no CYP3A4 induction).
Mechanism
Carbamazepine induces CYP3A4; alprazolam plasma levels fall by 50%. Loss of anxiolytic effect and withdrawal symptoms (anxiety, insomnia, tremor) are possible.
Symptoms
Return of anxiety, insomnia, tremor, sweating, tachycardia (withdrawal). With high carbamazepine doses, full return of panic disorder symptoms is possible.
Management
During carbamazepine therapy, increase alprazolam by 50% or switch to lorazepam/oxazepam (glucuronidated, no CYP3A4 dependence). Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Dual mechanism. Carbamazepine induces CYP3A4 and lowers amiodarone levels. Amiodarone blocks CYP3A4 and partially suppresses carbamazepine metabolism, so carbamazepine plasma levels may rise.
Symptoms
From amiodarone fall: atrial fibrillation symptoms return. From carbamazepine rise: ataxia, diplopia, nausea, hyponatraemia, drowsiness.
Management
Avoid the combination. Alternative anticonvulsants without induction: levetiracetam, lamotrigine. Alternative antiarrhythmic: beta-blocker for rate control or catheter ablation. If unavoidable, check carbamazepine plasma levels at 1–2 weeks.
Mechanism
Carbamazepine induces CYP3A4 and CYP2D6; amitriptyline plasma levels fall by 50–60%. Loss of antidepressant and analgesic effect is possible.
Symptoms
Return of depressive symptoms or neuropathic pain. In depression: relapse risk.
Management
During carbamazepine therapy, double amitriptyline with clinical efficacy monitoring. Alternative anticonvulsants without induction: levetiracetam, lamotrigine (no CYP3A4 induction).
Mechanism
Carbamazepine induces CYP3A4 – the main amlodipine metabolic route. Amlodipine plasma levels fall and the antihypertensive effect weakens.
Symptoms
Blood pressure returns to baseline or higher, headache. In angina, episodes reappear. Symptoms emerge 1–2 weeks after starting carbamazepine.
Management
During carbamazepine therapy, increase amlodipine 1.5- to 2-fold with blood pressure monitoring, or switch to an ACE-I (enalapril) or diuretic (hydrochlorothiazide). Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Carbamazepine induces CYP3A4 and P-glycoprotein – two apixaban clearance routes. Apixaban plasma levels fall and antithrombotic effect weakens.
Symptoms
The patient feels nothing. Stroke risk in atrial fibrillation rises, as do deep vein thrombosis and pulmonary embolism risks.
Management
Avoid the combination. Alternative anticoagulants: warfarin with INR monitoring or low molecular weight heparin. Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Carbamazepine induces CYP3A4 – the main atorvastatin metabolic route. Atorvastatin plasma levels fall by 30–60%; lipid-lowering effect drops proportionally.
Symptoms
The patient feels nothing. Laboratory: cholesterol and total cholesterol rise. In high cardiovascular risk patients, myocardial infarction and stroke risk increase.
Management
During carbamazepine therapy, increase atorvastatin 1.5- to 2-fold with lipid profile and creatine kinase monitoring, or switch to pravastatin (CYP3A4-independent). Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Carbamazepine induces CYP3A4 – the main cyclosporine metabolic route. Cyclosporine plasma levels drop sharply; immunosuppression weakens, raising transplant rejection risk.
Symptoms
Rejection symptoms depend on the organ: fever, graft tenderness, rising creatinine (kidney); jaundice and rising liver enzymes (liver); dyspnoea (heart, lungs). Symptoms appear 1–3 weeks after starting carbamazepine.
Management
Avoid the combination. Alternative anticonvulsants in transplant patients: levetiracetam, lamotrigine, or gabapentin (minimal CYP3A4 effect). If carbamazepine is unavoidable, measure cyclosporine levels 2–3 times weekly and increase the dose.
Mechanism
Clarithromycin blocks CYP3A4 – the main carbamazepine metabolic route. Carbamazepine plasma levels rise by 30–50%, with neurotoxicity risk.
Symptoms
Ataxia, diplopia, nausea, drowsiness, tremor. Severe cases include cardiac conduction abnormalities and coma. Symptoms appear within 3–5 days of co-administration.
Management
Avoid the combination. Alternative antibiotics: azithromycin or doxycycline (minimal CYP3A4 impact). If clarithromycin is needed, measure carbamazepine plasma levels at days 3 and 7.
Mechanism
Carbamazepine induces P-glycoprotein, the main dabigatran clearance route. Dabigatran plasma levels fall and anticoagulant effect weakens – stroke risk in atrial fibrillation rises.
Symptoms
The patient feels nothing. Stroke, deep vein thrombosis, and pulmonary embolism risks rise.
Management
Avoid the combination. Alternative anticoagulants: warfarin with INR monitoring or low molecular weight heparin for short courses. Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Diltiazem blocks CYP3A4 – the main carbamazepine metabolic route. Carbamazepine plasma levels rise 1.5-fold. Neurotoxicity risk emerges (ataxia, diplopia, sedation).
Symptoms
Ataxia, diplopia, nausea, drowsiness, tremor. Severe cases: cardiac conduction abnormalities and AV block.
Management
Avoid the combination. Alternative calcium channel blocker without CYP3A4 inhibition: amlodipine (with caution). If unavoidable, check carbamazepine level at 1 and 4 weeks.
Mechanism
Carbamazepine induces CYP3A4 and accelerates hepatic doxycycline metabolism. Doxycycline half-life shortens from 16 to 7 hours; plasma levels fall.
Symptoms
The patient feels nothing. Risk of subtherapeutic antimicrobial concentrations and treatment failure rises – particularly with pathogens at the susceptibility breakpoint.
Management
Increase doxycycline to 200 mg twice daily during the course (instead of standard 100 mg twice daily). Alternative antibiotics without induction-driven loss: a cephalosporin, amoxicillin, azithromycin. Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Carbamazepine induces CYP3A4 and accelerates ethinylestradiol metabolism. Combined oral contraceptive efficacy drops; pregnancies during regular use have been reported.
Symptoms
Breakthrough bleeding, missed periods, unplanned pregnancy. The patient feels no symptoms at the moment of dosing.
Management
Switch hormonal contraception to non-hormonal methods (copper IUD or barrier methods) for the duration of carbamazepine therapy. Alternatives: depot progesterone or a levonorgestrel IUD.
Mechanism
Carbamazepine induces CYP3A4 – a partial haloperidol clearance route. Haloperidol plasma levels fall by 50% and antipsychotic effect weakens.
Symptoms
Return of positive symptoms: hallucinations, delusions, agitation. In schizophrenia, risk of acute relapse.
Management
During carbamazepine therapy, increase haloperidol 1.5- to 2-fold under clinical monitoring. Alternative anticonvulsants without induction: sodium valproate, levetiracetam, lamotrigine (no CYP3A4 induction).
Mechanism
Carbamazepine is a CYP3A4 inducer. It lowers isotretinoin plasma levels, which can cause acne therapy failure. Additionally: both drugs are teratogens, absolutely contraindicated in pregnancy.
Symptoms
Recurrence of acne, no response to isotretinoin. In pregnancy on combination: severe foetal malformations (both drugs are teratogens).
Management
Avoid the combination. Alternative anticonvulsants without induction: levetiracetam, lamotrigine. Alternative acne therapy: antibiotics (doxycycline, azithromycin), topical retinoids, spironolactone in women. In women of reproductive age, mandatory dual contraception.
Mechanism
Carbamazepine is a potent CYP3A4 inducer. Quetiapine plasma levels fall by 75–85%, which can cause loss of therapeutic effect (psychosis or mania relapse).
Symptoms
Return of positive symptoms: hallucinations, delusions, agitation. In bipolar disorder: manic episode risk.
Management
During carbamazepine therapy, increase quetiapine 4- to 5-fold with clinical monitoring. Alternative anticonvulsants without induction: sodium valproate, lamotrigine, or levetiracetam.
Mechanism
Carbamazepine induces CYP3A4 and P-glycoprotein – two rivaroxaban clearance routes. Rivaroxaban plasma levels fall by 50%; anticoagulant effect weakens.
Symptoms
The patient feels nothing. Stroke risk in atrial fibrillation rises, as do deep vein thrombosis and pulmonary embolism risks.
Management
Avoid the combination. Alternative anticoagulants: warfarin with INR monitoring or low molecular weight heparin. Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Carbamazepine induces CYP3A4 – the main simvastatin metabolic route. Simvastatin plasma levels fall 5- to 10-fold; lipid-lowering effect drops proportionally.
Symptoms
The patient feels nothing. Laboratory: cholesterol and total cholesterol rise. In high cardiovascular risk patients, myocardial infarction and stroke risk increase.
Management
During carbamazepine therapy, increase simvastatin 2- to 3-fold with lipid profile and creatine kinase monitoring, or switch to pravastatin/rosuvastatin (metabolism less CYP3A4-dependent). Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Carbamazepine strongly induces CYP3A4 and P-glycoprotein. Tacrolimus plasma levels fall 2- to 3-fold; immunosuppression is lost, raising rejection risk.
Symptoms
Rejection symptoms depend on the organ: fever, graft tenderness, rising creatinine (kidney); jaundice and rising liver enzymes (liver). Symptoms appear 1–3 weeks after starting carbamazepine.
Management
Avoid the combination. Alternative anticonvulsants without induction: levetiracetam, lamotrigine, gabapentin. If carbamazepine is unavoidable, raise tacrolimus 2- to 3-fold with trough (C0) twice weekly.
Mechanism
Carbamazepine induces CYP1A2, which partly metabolises theophylline. Theophylline plasma levels fall by 25–50%; bronchodilator effect weakens.
Symptoms
Recurrence of asthma or COPD symptoms: dyspnoea, wheezing.
Management
During carbamazepine therapy, increase theophylline by 50% with level monitoring at 1–2 weeks. Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Verapamil blocks CYP3A4 – the main carbamazepine metabolic route. Carbamazepine plasma levels rise, with neurotoxicity risk.
Symptoms
Ataxia, diplopia, nausea, drowsiness, tremor. Severe cases include cardiac conduction abnormalities and AV block. Symptoms appear within 1–2 weeks.
Management
Avoid the combination. Alternative calcium channel blockers without CYP3A4 inhibition: amlodipine or diltiazem (use diltiazem with caution; it has a moderate CYP3A4 effect). If unavoidable, measure carbamazepine plasma levels at 1 and 4 weeks.
Mechanism
Carbamazepine strongly induces CYP2C9 and CYP3A4. Warfarin plasma levels fall by 50–70% over 2–4 weeks; anticoagulant effect weakens.
Symptoms
INR drops below target. Thromboembolic risk rises: deep vein thrombosis, pulmonary embolism, ischaemic stroke in atrial fibrillation.
Management
After starting carbamazepine, check INR every 1–2 weeks for the first month and titrate warfarin (usually 1.5- to 2-fold dose increase). On carbamazepine withdrawal, induction persists for 2–4 weeks – return warfarin gradually. Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Carbamazepine is a strong CYP3A4 inducer. Plasma oestradiol falls by 40–60%. On menopausal hormone therapy, menopausal symptoms may return; on combined oral contraceptives, unplanned pregnancy risk arises.
Symptoms
Return of vasomotor symptoms: hot flushes, night sweats, sleep disturbance. On oral contraceptives: breakthrough bleeding, conception risk.
Management
On menopausal hormone therapy, double the oestradiol dose or switch to transdermal forms (patch, gel — minimal hepatic metabolism). For contraception on carbamazepine, combined oral contraceptives are unsuitable — choose a levonorgestrel IUS, copper IUD, or depot medroxyprogesterone acetate.
Mechanism
No direct pharmacokinetic interaction. Mild additive CNS depression and haematologic toxicity: linezolid myelosuppression plus carbamazepine's rare agranulocytosis- and thrombocytopaenia-inducing activity.
Symptoms
Fatigue, confusion, frequent infections (from leukopenia), bleeding (from thrombocytopenia). Symptoms develop with linezolid courses over 14 days.
Management
For short linezolid courses (10–14 days) on stable carbamazepine, no adjustment needed. Check CBC at one week and at course end. For long-term linezolid (over 14 days), weekly CBC. Antibiotic alternative if needed: vancomycin (no myelosuppression).
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Boxed warning
FDA boxed warning: risk of aplastic anemia and agranulocytosis (approximately 5–8 times higher than general population). Additional warning: serious dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, especially in HLA-B*15:02 allele carriers. Genetic testing is recommended in patients of Asian ancestry before initiation.
FDA category D. Increases risk of neural tube defects (spina bifida, 1%), cleft palate, congenital heart defects, hypospadias. Women of reproductive age receive concomitant folic acid 4–5 mg daily. When possible, alternative antiepileptics (levetiracetam, lamotrigine) are used. Decision made jointly with neurologist and obstetrician.
Passes into breast milk at 25–60% of maternal plasma concentration. LactMed lists carbamazepine as generally compatible with breastfeeding under infant monitoring (sedation, vomiting, jaundice).
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Carbamazepine is evaluated for the following indications with varying evidence strength: Focal epilepsy (evidence tier A), Trigeminal neuralgia (evidence tier A), Bipolar disorder (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Carbamazepine (≥ 1 in 100): Dizziness, ataxia, drowsiness, Nausea, vomiting, Hyponatremia (SIADH), Mild leukopenia, Rash, Diplopia at peak levels. See the Safety section for uncommon and serious reactions.
FDA category D. FDA category D. Increases risk of neural tube defects (spina bifida, 1%), cleft palate, congenital heart defects, hypospadias. Women of reproductive age receive concomitant folic acid 4–5 mg daily. When possible, alternative antiepileptics (levetiracetam, lamotrigine) are used. Decision made jointly with neurologist and obstetrician.
Passes into breast milk at 25–60% of maternal plasma concentration. LactMed lists carbamazepine as generally compatible with breastfeeding under infant monitoring (sedation, vomiting, jaundice).
Carbamazepine is contraindicated in: Hypersensitivity to carbamazepine, oxcarbazepine, tricyclic antidepressants; Atrioventricular block; History of bone marrow depression; Acute intermittent porphyria; Combination with MAO inhibitors (14 days before and after therapy). Full list in the Safety section.
FDA boxed warning: risk of aplastic anemia and agranulocytosis (approximately 5–8 times higher than general population). Additional warning: serious dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, especially in HLA-B*15:02 allele carriers. Genetic testing is recommended in patients of Asian ancestry before initiation.
effective but requires regular monitoring of blood, liver, and plasma level. Risk of severe cutaneous reactions in HLA-B*15:02 carriers and teratogenicity in pregnancy.
not used for anxiety or neurotic disorders. Registered indications are epilepsy, trigeminal neuralgia, bipolar disorder.
one of the strongest CYP3A4 inducers. Reduces effectiveness of oral contraceptives, warfarin, many antibiotics, and immunosuppressants.