Systematic (IUPAC) name
Clinical data
Trade names Tegretol
AHFS/ monograph
MedlinePlus a682237
Pregnancy cat. D(US)
Legal status POM (UK) -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 80%
Protein binding 76%
Metabolism Hepatic—by CYP3A4, to active epoxide form (carbamazepine-10,11 epoxide)
Half-life 25–65 hours (after several doses 12-17 hours)
Excretion 2–3% excreted unchanged in urine
CAS number 298-46-4 YesY 85756-57-6
ATC code N03AF01
PubChem CID 2554
DrugBank DB00564
ChemSpider 2457 YesY
UNII 33CM23913M YesY
KEGG D00252 YesY
Chemical data
Formula C15H12N2O 
Mol. mass 236.269 g/mol
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

Carbamazepine (CBZ) is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It is also used off-label for a variety of indications, including attention-deficit hyperactivity disorder (ADHD), schizophrenia, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder and post-traumatic stress disorder.

It has been seen as safe for pregnant women to use carbamazepine as a mood stabilizer,[1] but, like other anticonvulsants, intrauterine exposure is associated with spina bifida[2] and neurodevelopmental problems.[3]


Medical uses

Carbamazepine is typically used for the treatment of seizure disorders and neuropathic pain.[4] It may be used as a second line treatment for bipolar disorder and along with antipsychotic agents in schizophrenia.[4]

In the United States, the FDA-approved indications are epilepsy (including partial seizures and tonic-clonic seizures), trigeminal neuralgia, and manic and mixed episodes of bipolar I disorder.[5] Although data are still lacking, carbamazepine appears to be as effective and safe as lithium for the treatment of bipolar disorder, both in the acute and maintenance phase.[6]

Adverse effects

Common adverse effects may include drowsiness, headaches and migraines, motor coordination impairment, and/or upset stomach. Carbamazepine preparations typically greatly decrease a person's alcohol tolerance.

Less common side-effects may include cardiac arrhythmias, blurry or double vision and/or the temporary loss of blood cells or platelets and in rare cases can cause aplastic anemia. With normal use, small reductions in white cell count and serum sodium are common; however, in rare cases, the loss of platelets may become life-threatening. In this case a doctor may recommend frequent blood tests during the first few months of use, followed by three to four tests per year for established patients. Additionally, carbamazepine may possibly exacerbate preexisting cases of hypothyroidism, so yearly thyroid function tests are advisable for persons taking the drug.

There are also rare reports of an auditory side-effect for carbamazepine use, whereby patients perceive sounds about a semitone lower than previously.[7][8][9] Thus, middle C would be heard as the note B3 just below it, and so on. The inverse effect (that is, notes sounding higher) has also been recorded.[10][11] This unusual side-effect is usually not noticed by most people, and quickly disappears after the person stops taking carbamazepine.

Carbamazepine increases the risk of developing lupus by 1.88.[12]

Oxcarbazepine, a derivative of carbamazepine, reportedly has fewer and less serious side-effects.

Carbamazepine may cause Syndrome of inappropriate antidiuretic hormone (SIADH), since it both increases the release and potentiates the action of ADH (vasopressin).

Carbamazepine may aggravate juvenile myoclonic epilepsy, so it is important to uncover any history of jerking, especially in the morning, before starting the drug. It may also aggravate other types of generalized seizure disorder, particularly absence seizures.[13]

In addition, carbamazepine has been linked to serious adverse cognitive anomalies, including EEG slowing[14] and cell apoptosis.[15]

The FDA informed health care professionals that dangerous or even fatal skin reactions (Stevens Johnson syndrome and toxic epidermal necrolysis), that can be caused by carbamazepine therapy, are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians.[16] In Europeans a large proportion of sensitivity is associated with HLA-B58.Researchers have also identified another genetic variant, HLA-A*3101 which has been shown to be a strong predictor of both mild and severe adverse reactions to carbamazepine among Japanese[17] and Europeans.[18]


Carbamazepine has a potential for drug interactions; caution should be used in combining other medicines with it, including other antiepileptics and mood stabilizers.[5] Lower levels of carbamazepine are seen when administrated with phenobarbital, phenytoin (Dilantin), or primidone (Mysoline). Carbamazepine, as a CYP450 inducer, may increase clearance of many drugs, decreasing their blood levels.[19] Drugs that are more rapidly metabolized with carbamazepine include warfarin (Coumadin), phenytoin (Dilantin), theophylline, and valproic acid (Depakote, Depakote ER, Depakene, Depacon).[5] Drugs that decrease the metabolism of carbamazepine or otherwise increase its levels include erythromycin,[20] cimetidine (Tagamet), propoxyphene (Darvon), and calcium channel blockers.[5] Carbamazepine also increases the metabolism of the hormones in birth control pills and can reduce their effectiveness, potentially leading to unexpected pregnancies.[5]

Valproic acid and valnoctamide both inhibit microsomal epoxide hydrolase (mEH), the enzyme responsible for the breakdown of carbamazepine-10,11 epoxide into inactive metabolites.[21] By inhibiting mEH, valproic acid and valnoctamide cause a buildup of the active metabolite, prolonging the effects of carbamazepine and delaying its excretion.

Grapefruit juice raises the bioavailability of carbamazepine by inhibiting CYP3A4 enzymes in the gut wall and in the liver.


Carbamazepine exhibits autoinduction: it induces the expression of the hepatic microsomal enzyme system CYP3A4, which metabolizes carbamazepine itself. Upon initiation of carbamazepine therapy, concentrations are predictable and follow their respective baseline clearance/half-life values that have been established for the specific patient. However, after enough carbamazepine has been presented to the liver tissue, the CYP3A4 activity increases, speeding up drug clearance and shortening the half-life. Autoinduction will continue with subsequent increases in dose but will usually reach a plateau within 5–7 days of a maintenance dose. Increases in dose at a rate of 200 mg every 1–2 weeks may be required to achieve a stable seizure threshold. Stable carbamazepine concentrations occur usually within 2–3 weeks after initiation of therapy.[22]

Mechanism of action

The mechanism of action of carbamazepine and its derivatives is relatively well understood. Voltage-gated sodium channels are the molecular pores that allow brain cells (neurons) to generate action potentials, the electrical events that allow neurons to communicate over long distances. After the sodium channels open to start the action potential, they inactivate, in essence closing the channel. Carbamazepine stabilizes the inactivated state of sodium channels, meaning that fewer of these channels are available to subsequently open, making brain cells less excitable (less likely to fire). Carbamazepine has also been shown to potentiate GABA receptors made up of alpha1, beta2, gamma2 subunits.[23]


Carbamazepine was discovered by chemist Walter Schindler at J.R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953.[24] Schindler then synthesized the drug in 1960, before its anti-epileptic properties had been discovered.

Carbamazepine was first marketed as a drug to treat trigeminal neuralgia (formerly known as tic douloureux) in 1962. It has been used as an anticonvulsant in the UK since 1965, and has been approved in the U.S. since 1974.

In 1971, Drs. Takezaki and Hanaoka first used carbamazepine to control mania in patients refractory to antipsychotics (Lithium was not available in Japan at that time). Dr. Okuma, working independently, did the same thing with success. As they were also epileptologists, they had some familiarity with the anti-aggression effects of this drug. Carbamazepine would be studied for bipolar disorder throughout the 1970s.[25]

Brand names

Carbamazepine has been sold under the names Biston, Calepsin, Carbatrol, Epitol, Equetro, Finlepsin, Sirtal, Stazepine, Telesmin, Tegretol, Teril, Timonil, Trimonil, Epimaz, Carbama/Carbamaze (New Zealand), Amizepin (Poland),Carzine (Kolkata), Karbapin (Serbia), Hermolepsin (Sweden), Degranol (South Africa).,[26] and Tegretal (Chile, Germany).[27]

See also


Carbamazepine syn.png

Schindler, W.; 1960, U.S. Patent 2,948,718.

Carbamazepine is a dibenzazepine.



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Look at other dictionaries:

  • Carbamazépine — Général Nom IUPAC …   Wikipédia en Français

  • Carbamazepine — Carbamazépine Carbamazépine Général Nom IUPAC …   Wikipédia en Français

  • carbamazepine — noun Etymology: carbamoyl (a radical of carbamic acid) + azepine (as in benzodiazepine) Date: 1966 a tricyclic anticonvulsant and analgesic C15H12N2O used in the treatment of trigeminal neuralgia and epilepsy …   New Collegiate Dictionary

  • carbamazepine — /kahr beuh maz euh peen /, n. Pharm. a white to whitish toxic powder, C15H12N2O, used as an analgesic in the treatment of trigeminal neuralgia and as an anticonvulsant. [carbam(oyl) + azepine, components of the chemical name] * * * …   Universalium

  • carbamazepine — noun An anticonvulsant drug used in the treatment of epilepsy …   Wiktionary

  • carbamazepine — An anticonvulsant; also useful in alleviating the pain of trigeminal neuralgia and other neurogenic pain syndromes. * * * car·ba·maz·e·pine .kär bə maz ə .pēn n a tricyclic anticonvulsant and analgesic C15H12N2O used in the treatment of… …   Medical dictionary

  • carbamazepine — n. anticonvulsant drug used to treat epilepsy and to relieve pain related to trigeminal neuralgia …   English contemporary dictionary

  • carbamazepine — [ˌkα:bə meɪzɪpi:n] noun Medicine a synthetic compound used as an anticonvulsant and analgesic drug. Origin 1960s: from carbo + amide, on the pattern of benzodiazepine …   English new terms dictionary

  • carbamazepine — car·ba·maz·e·pine …   English syllables

  • carbamazepine — n. an anticonvulsant drug used in the treatment of epilepsy and bipolar affective disorder and to relieve the pain of trigeminal neuralgia. Common side effects include drowsiness, dizziness, and muscular incoordination; abnormalities of liver and …   The new mediacal dictionary

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