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Systematic (IUPAC) name
Clinical data
Trade names Tegretol
AHFS/ monograph
MedlinePlus a682237
Licence data US Daily Med:link
Pregnancy cat.
Legal status
Routes Oral
Pharmacokinetic data
Bioavailability ~100%[1]
Protein binding 70-80%[1]
Metabolism Hepatic—by CYP3A4, to active epoxide form (carbamazepine-10,11 epoxide)[1]
Half-life 36 hours (single dose), 16-24 hours (repeated dosing)[1]
Excretion Urine (72%), feces (28%)[1]
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
 YesY (what is this?)  (verify)
Tegretol 200-mg CR (made in NZ)

Carbamazepine (CBZ) (Tegretol, Equetro) is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. Off-label uses include attention-deficit hyperactivity disorder, schizophrenia, phantom limb syndrome, complex regional pain syndrome, borderline personality disorder, and post-traumatic stress disorder.

It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[2]

Medical uses[edit]

Carbamazepine is typically used for the treatment of seizure disorders and neuropathic pain.[3] It is used off-label as a second-line treatment for bipolar disorder and as an adjunct, never alone, with an antipsychotic in some cases of schizophrenia when treatment with a conventional antipsychotic alone has failed.[3][4]

In the United States, the FDA-approved indications are epilepsy (including partial seizures, generalized tonic-clonic seizures and mixed seizures), trigeminal neuralgia, and manic and mixed episodes of bipolar I disorder.[5]

Adverse effects[edit]

In the US, the label for carbamazepine contains warnings concerning:

  • serious and sometimes fatal skin reactions in people who have a specific version of the HLA-B protein, namely the 1502 allele, including toxic epidermal necrolysis and Stevens-Johnson syndrome (SJS), reported in patients receiving carbamazepine therapy. These reactions are estimated to occur in 1–6 per 10,000 new users of carbamazepine in countries with mainly Caucasian populations; but the risk in some Asian populations is estimated to be about10 times higher.[1]
  • effects on the body's production of red blood cells, white blood cells, and platelets: rarely, there are major effects of aplastic anemia and agranulocytosis reported and more commonly, there are minor changes such as decreased leukocyte or platelet counts, that do not progress to more serious problems.[1]
  • increased risks of suicide[1]
  • risk of seizures, if the person stops taking the drug abruptly[1]
  • risks to the fetus in women who are pregnant, specifically congenital malformations like spina bifida, and developmental disorders.[1] [6]

Common adverse effects may include drowsiness, dizziness, headaches and migraines, motor coordination impairment, nausea, vomiting and/or constipation. Alcohol use while taking carbamazepine may lead to enhanced depression of the central nervous system.[1] Less common side effects may include increased risk of seizures in people with mixed seizure disorders,[7] cardiac arrhythmias, blurry or double vision.[1] Also, rare case reports of an auditory side effect have been made, whereby patients perceive sounds about a semitone lower than previously; this unusual side effect is usually not noticed by most people, and disappears after the person stops taking carbamazepine.[8]


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), which can result in breakthrough seizure activity. Carbamazepine, as a CYP450 inducer, may increase clearance of many drugs, decreasing their concentration in the blood to subtherapeutic levels and reducing their desired effects.[9] Drugs that are more rapidly metabolized with carbamazepine include warfarin (Coumadin), lamotrigine (Lamictal), 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,[10] 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] As a drug that induces cytochrome P450 enzymes, it accelerates elimination of many benzodiazepines and decreases their action.[11]

Valproic acid and valnoctamide both inhibit microsomal epoxide hydrolase (MEH), the enzyme responsible for the breakdown of carbamazepine-10,11 epoxide into inactive metabolites.[12] By inhibiting MEH, valproic acid and valnoctamide cause a build-up 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.[1]


Carbamazepine is relatively slowly but well absorbed after oral administration. Its plasma half-life is about 30 hours when it is given as single dose, but it is a strong inducer of hepatic enzymes and the plasma half-life shortens to about 15 hours when it is given repeatedly.[medical citation needed]

Mechanism of action[edit]

The mechanism of action of carbamazepine and its derivatives is relatively well understood. Carbamazepine stabilizes the inactivated state of voltage-gated sodium channels, making fewer of these channels available to subsequently open. This leaves the affected cells less excitable until the drug dissociates.[citation needed] Carbamazepine has also been shown to potentiate GABA receptors made up of alpha1, beta2, and gamma2 subunits.[13] This mechanism may contribute to its efficacy in neuropathic pain and manic-depressive illness.


Carbamazepine was discovered by chemist Walter Schindler at J.R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953.[14] Schindler then synthesized the drug in 1960, before its antiepileptic properties had been discovered. It was first marketed as a drug to treat trigeminal neuralgia (formerly known as tic douloureux) in 1962. It has been used as an anticonvulsant and antiepileptic in the UK since 1965, and has been approved in the US 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 antiaggression effects of this drug. Carbamazepine was studied for bipolar disorder throughout the 1970s.[15]

Environmental fate[edit]

Carbamazepine has been detected in wastewater effluent.[16]:224 Field and laboratory studies have been conducted to understand the accumulation of carbamazepine in food plants grown in soil treated with sludge, which vary with respect to the concentrations of carbamazepine present in sludge and in the concentrations of sludge in the soil; taking into account only studies that used concentrations normally found, a 2014 review found that "the accumulation of carbamazepine into plants grown in soil amended with biosolids poses a de minimis risk to human health according to the approach."[16]:227

Brand names[edit]

Carbamazepine has been sold under the names Biston, Calepsin, Carbatrol, Epitol, Equetro, Finlepsin, Sirtal, Stazepine, Seizunil, Telesmin, Tegretol, Epitab XR, Teril, Timonil, Trimonil, Epimaz, Carbama/Carbamaze, Amizepin, Carzine, Mazetol, Neurotop, Tegrital, Tegrita, Zeptol, Karbapin, Hermolepsin, Degranol, and Tegretal.[17]


  1. ^ a b c d e f g h i j k l m "Carbamazepine Drug Label". 
  2. ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014. 
  3. ^ a b "Carbamazepine". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  4. ^ Ceron-Litvoc D, Soares BG, Geddes J, Litvoc J, de Lima MS (January 2009). "Comparison of carbamazepine and lithium in treatment of bipolar disorder: a systematic review of randomized controlled trials". Hum Psychopharmacol 24 (1): 19–28. doi:10.1002/hup.990. PMID 19053079. 
  5. ^ a b c d e Lexi-Comp (February 2009). "Carbamazepine". The Merck Manual Professional. Archived from the original on 2010-11-18.  Retrieved on May 3, 2009.
  6. ^ Jentink, J; Dolk, H, Loane, MA, Morris, JK, Wellesley, D, Garne, E, de Jong-van den Berg, L, EUROCAT Antiepileptic Study Working, Group (2010-12-02). "Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study". BMJ (Clinical research ed.) 341: c6581. doi:10.1136/bmj.c6581. PMC 2996546. PMID 21127116. 
  7. ^ Lige Liu, Thomas Zheng, Margaret J. Morris, Charlott Wallengren, Alison L. Clarke, Christopher A. Reid, Steven Petrou and Terence J. O'Brien (2006). "The Mechanism of Carbamazepine Aggravation of Absence Seizures". JPET 319 (2): 790–798. doi:10.1124/jpet.106.10496. PMID 16895979. 
  8. ^ Tateno A, et al. Carbamazepine-induced transient auditory pitch-perception deficit. Pediatr Neurol. 2006 Aug;35(2):131-4. PMID 16876011
  9. ^ "eMedicine - Toxicity, Carbamazepine". Archived from the original on 2008-08-04. 
  10. ^ Stafstrom CE, Nohria V, Loganbill H, Nahouraii R, Boustany RM, DeLong GR (January 1995). "Erythromycin-induced carbamazepine toxicity: a continuing problem". Arch Pediatr Adolesc Med 149 (1): 99–101. doi:10.1001/archpedi.1995.02170130101025. PMID 7827672. Archived from the original on 2010-11-18. 
  11. ^ Moody D (2004). "Drug interactions with benzodiazepines". In Raymon LP, Mozayani A (eds.). Handbook of Drug Interactions: a Clinical and Forensic Guide. Humana. pp. 3–88. ISBN 1-58829-211-8. 
  12. ^ Gonzalez, Frank J.; Robert H. Tukey (2006). "Drug Metabolism". In Laurence Brunton, John Lazo, Keith Parker (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. p. 79. ISBN 978-0-07-142280-2. 
  13. ^ Granger, P. et al. Modulation of the gamma-aminobutyric acid type A receptor by the antiepileptic drugs carbamazepine and phenytoin. Mol. Pharmacol. 47, 1189–1196 (1995).
  14. ^ Schindler W, Häfliger F (1954). "Über Derivate des Iminodibenzyls". Helvetica Chimica Acta 37 (2): 472–83. doi:10.1002/hlca.19540370211. 
  15. ^ Okuma T, Kishimoto A (February 1998). "A history of investigation on the mood stabilizing effect of carbamazepine in Japan". Psychiatry Clin. Neurosci. 52 (1): 3–12. doi:10.1111/j.1440-1819.1998.tb00966.x. PMID 9682927. 
  16. ^ a b Prosser RS, Sibley PK2. Human health risk assessment of pharmaceuticals and personal care products in plant tissue due to biosolids and manure amendments, and wastewater irrigation. Environ Int. 2014 Dec 5;75C:223-233. doi: 10.1016/j.envint.2014.11.020. PMID 25486094
  17. ^

External links[edit]