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Identification
NameCarbamazepine
Accession NumberDB00564  (APRD00337)
Typesmall molecule
Groupsapproved, investigational
Description

An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
5-Carbamoyl-5H-dibenz(b,f)azepineNot AvailableNot Available
CarbamazepinGermanINN
CarbamazepinaSpanishINN
CarbamazépineFrenchINN
CarbamazepinumLatinINN
CBZNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ActebralSanofi-Aventis
AnlepticSquare
BistonZentiva
CarbamatAstraZeneca
CarbatrolNot Available
EpitolTeva
EquetroValidus
NeurotopGerot
TEGretolNovartis
TégrétolNovartis
TEGretol ChewtabsNot Available
TEGretol-CRNovartis
TEGretol-XRNovartis
TerilTaro
TimonilDesitin
VersitolMicro Synapse
VersizurMicro Labs
Brand mixturesNot Available
Categories
CAS number298-46-4
WeightAverage: 236.2686
Monoisotopic: 236.094963016
Chemical FormulaC15H12N2O
InChI KeyFFGPTBGBLSHEPO-UHFFFAOYSA-N
InChI
InChI=1S/C15H12N2O/c16-15(18)17-13-7-3-1-5-11(13)9-10-12-6-2-4-8-14(12)17/h1-10H,(H2,16,18)
IUPAC Name
2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene-2-carboxamide
SMILES
NC(=O)N1C2=CC=CC=C2C=CC2=CC=CC=C12
Mass Specshow(7.72 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzazepines
SubclassDibenzazepines
Direct parentDibenzazepines
Alternative parentsAzepines; Benzene and Substituted Derivatives; Tertiary Amines; Polyamines
Substituentsazepine; benzene; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the dibenzazepines. These are compounds with two benzene rings connected by an azepine ring.
Pharmacology
IndicationFor the treatment of epilepsy and pain associated with true trigeminal neuralgia.
PharmacodynamicsCarbamazepine, an anticonvulsant structurally similar to tricyclic antidepressants, is used to treat partial seizures, tonic-clonic seizures, pain of neurologic origin such as trigeminal neuralgia, and psychiatric disorders including manic-depressive illness and aggression due to dementia. The response to carbamazepine is variable and may be due to its variable transport, especially across the blood-brain-barrier. The transporter that may confer drug resistance is RALBP1.
Mechanism of actionCarbamazepine inhibits sustained repetitive firing by blocking use-dependent sodium channels. Pain relief is believed to be associated with blockade of synaptic transmission in the trigeminal nucleus and seizure control with reduction of post-tetanic potentiation of synaptic transmission in the spinal cord. Carbamazepine also possesses anticholinergic, central antidiuretic, antiarrhythmic, muscle relaxant, antidepressant (possibly through blockade of norepinephrine release), sedative, and neuromuscular-blocking properties.
AbsorptionIn clinical studies, carbamazepine suspension, conventional tablets, and extended-release tablets delivered equivalent amounts of drug to the systemic circulation. However, it has been observed that the suspension is somewhat faster absorbed. Furthermore, the extended-release tablet is slightly slower than the conventional tablet. The bioavailability of the extended-release tablet is 89%, compared to the suspension. Plasma levels of carbamazepine are variable. The time to peak concentration for the different formulations are as follows: Suspension = 1.5 hours; Conventional tablets = 4-5 hours; Extended-release tablets = 3-12 hours.
Volume of distributionNot Available
Protein binding76% bound to plasma proteins.
Metabolism

Hepatic. CYP3A4 is the primary isoform responsible for the formation of carbamazepine-10,11-epoxide. This metabolite is active and shown to be equipotent to carbamazepine as an anticonvulsant. Carbamazepine is more rapidly metabolized to the aforementioned metabolite in younger patients than in adults. It also undergoes glucuronidation via UGT2B7, however this finding has been disputed.

SubstrateEnzymesProduct
Carbamazepine
10,11-EpoxycarbamazepineDetails
Carbamazepine
3-hydroxycarbamazepineDetails
Carbamazepine
Not Available
Carbamazepine 2,3-epoxideDetails
3-hydroxycarbamazepine
2,3-DihydroxycarbamazepineDetails
Carbamazepine 2,3-epoxide
Not Available
2-hydroxycarbamazepineDetails
2-hydroxycarbamazepine
2-hydroxyiminostilbeneDetails
2-hydroxyiminostilbene
Not Available
Carbamazepine iminoquinoneDetails
2-hydroxycarbamazepine
Not Available
2,3-DihydroxycarbamazepineDetails
2,3-Dihydroxycarbamazepine
Not Available
Carbamazepine-O-quinoneDetails
10,11-Epoxycarbamazepine
10,11-DihydroxycarbamazepineDetails
Carbamazepine 2,3-epoxide
Not Available
3-hydroxycarbamazepineDetails
Route of elimination72% of the dose is in the urine while 28% is in the feces. Hydroxylated and conjugated metabolites are largely what was recovered in the urine. 3% of the dose is recovered as unchanged carbamazepine.
Half lifeInitial half-life values range from 25-65 hours, decreasing to 12-17 hours on repeated doses.
ClearanceNot Available
ToxicityMild ingestions cause vomiting, drowsiness, ataxia, slurred speech, nystagmus, dystonic reactions, and hallucinations. Severe intoxications may produce coma, seizures, respiratory depression, and hypotension
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Carbamazepine Metabolism PathwayDrug metabolismSMP00634
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Sodium channel protein type 1 subunit alpha
Gene symbol: SCN1A
UniProt: P35498
rs3812718 Not AvailableIVS5N + 5 G>ACarbamazepine resistant therapy, higher maintenance dose24052718
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Heat shock 70 kDa protein 1-like
Gene symbol: HSPA1L
UniProt: P34931
rs2227956 Not AvailableT alleleHypersensitivity reaction, mild erythematous skin rashes, macropapular eruption, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis16538175
Heat shock 70 kDa protein 1A/1B
Gene symbol: HSPA1A
UniProt: P08107
rs506770 Not AvailableC alleleHypersensitivity reaction, mild erythematous skin rashes, macropapular eruption, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis16538175
Heat shock 70 kDa protein 1A/1B
Gene symbol: HSPA1A
UniProt: P08107
rs1043620 Not AvailableC alleleHypersensitivity reaction, mild erythematous skin rashes, macropapular eruption, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis16538175
HLA class I histocompatibility antigen, B-15 alpha chain
Gene symbol: HLA-B
UniProt: P30464
rs3130690 Not AvailableT alleleStevens-Johnson syndrome (SJS), toxic epidermal necrolysis16538176
HLA class I histocompatibility antigen, A-31 alpha chain
Gene symbol: HLA-A
UniProt: P16189
rs1264511 Not AvailableG alleleMacropapular eruption16538176
Promotilin
Gene symbol: MLN
UniProt: P12872
rs2894342 Not AvailableA alleleHypersensitivity syndrome16538176
Flotillin-1
Gene symbol: FLOT1
UniProt: O75955
rs3909184 HLA-B*1502G > CPatients with the CG or GG genotype (in Asian patients) were at a higher risk of Steven-Johnson Syndrome compared to those with the CC genotype (non-carriers of HLA-b*1502)18637831
Mucin-21
Gene symbol: MUC21
UniProt: Q5SSG8
rs2844682 HLA-B*1502G>APatients with the AG or GG genotype (in Asian patients) were at a higher risk of Steven-Johnson Syndrome compared to those with the AA genotype18637831
Flotillin-1
Gene symbol: FLOT1
UniProt: O75955
rs3909184 HLA-B*1502G > CPatients with the CG or GG genotype (in Asian patients) were at a higher risk of Steven-Johnson Syndrome compared to those with the CC genotype (non-carriers of HLA-b*1502)15057820
Mucin-21
Gene symbol: MUC21
UniProt: Q5SSG8
rs2844682 HLA-B*1502G>APatients with the AG or GG genotype (in Asian patients) were at a higher risk of Steven-Johnson Syndrome compared to those with the AA genotype15057820
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9962
Blood Brain Barrier + 0.9958
Caco-2 permeable + 0.6538
P-glycoprotein substrate Non-substrate 0.6466
P-glycoprotein inhibitor I Non-inhibitor 0.8748
P-glycoprotein inhibitor II Non-inhibitor 0.8381
Renal organic cation transporter Non-inhibitor 0.8177
CYP450 2C9 substrate Non-substrate 0.7466
CYP450 2D6 substrate Substrate 0.884
CYP450 3A4 substrate Non-substrate 0.6204
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.9232
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8222
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7358
Ames test Non AMES toxic 0.5554
Carcinogenicity Non-carcinogens 0.8848
Biodegradation Not ready biodegradable 0.978
Rat acute toxicity 2.1131 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9653
hERG inhibition (predictor II) Non-inhibitor 0.8734
Pharmacoeconomics
Manufacturers
  • Shire development inc
  • Validus pharmaceuticals inc
  • Taro pharmaceutical industries ltd
  • Wockhardt eu operations (swiss) ag
  • Novartis pharmaceuticals corp
  • Taro pharmaceuticals usa inc
  • Cadista pharmaceuticals inc
  • Torrent pharmaceuticals ltd
  • Teva pharmaceuticals usa inc
  • Actavis elizabeth llc
  • Apotex inc etobicoke site
  • Inwood laboratories inc sub forest laboratories inc
  • Pliva inc
  • Usl pharma inc
  • Warner chilcott div warner lambert co
Packagers
Dosage forms
FormRouteStrength
Capsule, extended releaseOral100 mg, 200 mg, 300 mg
SuspensionOral100 mg/5 mL
TabletOral200 mg
Tablet, chewableOral100 mg
Tablet, extended releaseIrrigation100 mg, 200 mg, 400 mg
Prices
Unit descriptionCostUnit
Equetro 300 mg capsule2.65USDcapsule
TEGretol XR 400 mg 12 Hour tablet2.42USDtablet
Carbamazepine powder2.26USDg
Tegretol xr 400 mg tablet2.19USDtablet
Carbatrol 100 mg 12 Hour Capsule2.18USDcapsule
Equetro 200 mg capsule2.15USDcapsule
CarBAMazepine 400 mg 12 Hour tablet2.05USDtablet
Carbatrol 300 mg 12 Hour Capsule1.95USDcapsule
Carbatrol 200 mg 12 Hour Capsule1.92USDcapsule
Carbatrol er 100 mg capsule1.84USDcapsule
Carbatrol er 200 mg capsule1.84USDcapsule
Carbatrol er 300 mg capsule1.84USDcapsule
Equetro 100 mg capsule1.74USDcapsule
TEGretol XR 200 mg 12 Hour tablet1.45USDtablet
Tegretol xr 200 mg tablet1.1USDtablet
CarBAMazepine 200 mg 12 Hour tablet1.03USDtablet
TEGretol XR 100 mg 12 Hour tablet0.97USDtablet
Tegretol Cr 400 mg Sustained-Release Tablet0.84USDtablet
Tegretol 200 mg tablet0.75USDtablet
Tegretol xr 100 mg tablet0.55USDtablet
Tegretol Cr 200 mg Sustained-Release Tablet0.42USDtablet
Mylan-Carbamazepine Cr 400 mg Sustained-Release Tablet0.4USDtablet
Pms-Carbamazepine-Cr 400 mg Sustained-Release Tablet0.4USDtablet
Sandoz Carbamazepine Cr 400 mg Sustained-Release Tablet0.4USDtablet
Tegretol 200 mg Chewable Tablet0.34USDtablet
Carbamazepine 200 mg tablet0.31USDtablet
Epitol 200 mg tablet0.3USDtablet
CarBAMazepine 100 mg Chew Tabs0.25USDtab
Mylan-Carbamazepine Cr 200 mg Sustained-Release Tablet0.2USDtablet
Pms-Carbamazepine-Cr 200 mg Sustained-Release Tablet0.2USDtablet
Sandoz Carbamazepine Cr 200 mg Sustained-Release Tablet0.2USDtablet
Tegretol 100 mg Chewable Tablet0.17USDtablet
CarBAMazepine 100 mg/5ml Suspension0.16USDml
Pms-Carbamazepine 200 mg Chewable Tablet0.16USDtablet
Sandoz Carbamazepine 200 mg Chewable Tablet0.16USDtablet
Taro-Carbamazepine 200 mg Chewable Tablet0.16USDtablet
Apo-Carbamazepine 200 mg Tablet0.08USDtablet
Novo-Carbamaz 200 mg Tablet0.08USDtablet
Nu-Carbamazepine 200 mg Tablet0.08USDtablet
Pms-Carbamazepine 100 mg Chewable Tablet0.08USDtablet
Sandoz Carbamazepine 100 mg Chewable Tablet0.08USDtablet
Taro-Carbamazepine 100 mg Chewable Tablet0.08USDtablet
Tegretol 20 mg/ml Suspension0.08USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States69772532004-05-192024-05-19
United States52846621994-02-082011-02-08
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point204-206Schindier, W.; U.S. Patent 2,948,718; August 9, 1960; assigned to Geigy Chemical Corporation.
water solubility17.7 mg/LNot Available
logP2.45DAL POZZO,A ET AL. (1989)
Predicted Properties
PropertyValueSource
water solubility1.52e-01 g/lALOGPS
logP2.1ALOGPS
logP2.77ChemAxon
logS-3.2ALOGPS
pKa (strongest acidic)15.96ChemAxon
pKa (strongest basic)-3.8ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count1ChemAxon
polar surface area46.33ChemAxon
rotatable bond count0ChemAxon
refractivity71.89ChemAxon
polarizability25ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Ketan Dhansukhlal Vyas, Wajid Sajjad Jafri, Ashok Krishna Kulkarni, “Process for preparing carbamazepine from iminostilbene.” U.S. Patent US6245908, issued February, 1998.

US6245908
General Reference
  1. Staines AG, Coughtrie MW, Burchell B: N-glucuronidation of carbamazepine in human tissues is mediated by UGT2B7. J Pharmacol Exp Ther. 2004 Dec;311(3):1131-7. Epub 2004 Aug 3. Pubmed
  2. Sisodiya SM, Goldstein DB: Drug resistance in epilepsy: more twists in the tale. Epilepsia. 2007 Dec;48(12):2369-70. Pubmed
External Links
ResourceLink
KEGG DrugD00252
KEGG CompoundC06868
PubChem Compound2554
PubChem Substance46507583
ChemSpider2457
ChEBI3387
ChEMBLCHEMBL108
Therapeutic Targets DatabaseDAP000129
PharmGKBPA448785
Drug Product Database2241882
RxListhttp://www.rxlist.com/cgi/generic/carbam.htm
Drugs.comhttp://www.drugs.com/carbamazepine.html
WikipediaCarbamazepine
ATC CodesN03AF01
AHFS Codes
  • 28:12.92
PDB EntriesNot Available
FDA labelshow(55.9 KB)
MSDSshow(71.6 KB)
Interactions
Drug Interactions
Drug
AbirateroneStrong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
AcenocoumarolCarbamazepine may decrease the anticoagulant effect of acenocoumarol by decreasing its serum concentration.
AlprazolamCarbamazepine may decrease the effect of the benzodiazepine, alprazolam.
AminophyllineCarbamazepine may decrease the serum concentration of aminophylline. Aminophylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.
AmitriptylineCarbamazepine may decrease the serum concentration of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if carbamazepine is initiated, discontinued or dose changed.
AnisindioneCarbamazepine may decrease the anticoagulant effect of anisindione by decreasing its serum concentration.
AprepitantThe CYP3A4 inducer, carbamazepine, may decrease the effect of aprepitant.
AripiprazoleCarbamazepine, a strong CYP3A4 inducer, may decrease the serum concentration of aripiprazole by increasing its metabolism.
AsenapineCarbamazepine is a CYP1A2 inducer that decreases asenapine's exposure by 20%.
AtorvastatinCarbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of atorvastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if carbamazepine is initiated, discontinued or dose changed.
AtracuriumDecreases the effect of muscle relaxant
BendamustineDecreases levels of bendamustine by affecting CYP1A2 hepatic enzyme metabolism. May increase concentrations of active metabolites.
BoceprevirStrong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
BupropionCarbamazepine, a strong CYP2B6 inducer, may increase the metabolism of bupropion. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bupropion if carbamazepine is initiated, discontinued or dose changed.
CabazitaxelConcomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
CimetidineCimetidine may increase the serum concentration of carbamazepine during the first few days of concomitant therapy. Monitor for changes in the therapeutic and adverse effects of carbamazepine if cimetidine is initiated, discontinued or dose changed.
ClarithromycinClarithromycin may decrease the metabolism of carbamazepine. Monitor for changes in the therapeutic or adverse effects of carbamazepine if clarithromycin is initiated, discontinued or dose changed.
ClozapineCarbamazepine may decrease the serum concentration of clozapine by increasing its metabolism. Concomitant therapy should also be avoided due to increased risk of bone marrow suppression. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if carbamazepine is initiated, discontinued or dose changed.
CyclosporineCarbamazepine may decrease the therapeutic effect of cyclosporine.
Dabigatran etexilateP-Glycoprotein inducers such as carbamazepine may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
DabrafenibStrong CYP3A4 inducers may decrease levels of dabrafenib. Consider alternate therapy.
DanazolDanazol may decrease the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of carbamazepine if danazol is initiated, discontinued or dose changed.
DelavirdineThe anticonvulsant, carbamazepine, decreases the effect of delavirdine.
DesipramineCarbamazepine may decrease the serum concentration of the tricyclic antidepressant, desipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if carbamazepine is initiated, discontinued or dose changed.
DextropropoxyphenePropoxyphene increases the effect of carbamazepine
DicoumarolCarbamazepine may decrease the anticoagulant effect of dicumarol by decreasing its serum concentration.
DiltiazemCarbamazepine may decrease the serum concentration of diltiazem by increasing its metabolism. Diltiazem may increase the serum concentration of carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if dosages are changed.
Doxacurium chlorideDecreases the effect of muscle relaxant
DoxepinCarbamazepine may decrease the serum concentration of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if carbamazepine is initiated, discontinued or dose changed.
DoxycyclineThe anticonvulsant, carbamazepine, may decrease the therapeutic effect of doxycycline.
DyphyllineCarbamazepine may decrease the serum concentration of diphylline. Diphylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.
EltrombopagAffects hepatic CYP1A2 metabolism, will decrease effect/level of eltrombopag. Affects hepatic CYP2C9/10 metabolism, will decrease effect/level of eltrombopag.
ErythromycinThe macrolide, erythromycin, may increase the effect of carbamazepine.
Estradiol valerate/DienogestAffects CYP3A4 metabolism, decreases or effects levels of Estradiol valerate/Dienogest.
Ethinyl EstradiolCarbamazepine may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be relied on alone during concomitant therapy with carbamazepine.
EtravirineCarbamazepine, when used concomitantly with certain NNRTIs (ie. efavirenz), may experience a decrease in serum concentration. Etravirine, and other NNRTIs, when used concomitantly with carbamazepine, may experience an increase in serum concentration. It is recommended to avoid this combination.
EzogabineEzogabine increases the clearance of carbamazepine (30%). The mechanism of this interaction is unknown.
FelbamateDecreased effect of both products
FelodipineCarbamazepine may increase the metabolism of felodipine. Monitor for changes in the therapeutic and adverse effects of felodipine if carbamazepine is initiated, discontinued or dose changed.
FluconazoleFluconazole may increase the therapeutic and adverse effects of carbamazepine.
FluoxetineCarbamazepine may decrease the serum concentration of fluoxetine by increasing its metabolism. Fluoxetine may increase the serum concentration of carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or doses are changed.
FluvoxamineFluvoxamine increases the effect of carbamazepine
GefitinibThe CYP3A4 inducer, carbamazepine, may decrease the serum concentration and therapeutic effects of gefitinib.
HaloperidolCarbamazepine may decrease the serum concentration of haloperidol by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of haloperidol if carbamazepine is initiated, discontinued or dose changed.
ImatinibCarbamazepine, a strong CYP3A4 inducer, may increase the metabolism of imatinib. Imatinib, a strong CYP3A4 inhibitor, may increase the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose changed.
ImipramineCarbamazepine may decrease the serum concentration of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if carbamazepine is initiated, discontinued or dose changed.
IndinavirIndinavir increases the effect and toxicity of carbamazepine
IsoniazidCarbamazepine effect is increased as is isoniazid toxicity
IsotretinoinIsotretinoine decreases the effect of carbamazepine
ItraconazoleItraconazole may increase the effect of carbamazepine.
IvacaftorStrong CYP3A4 inducers may decrease levels of ivacaftor. Monitor concomitant therapy closely.
JosamycinThe macrolide, josamycin, may increase the effect of carbamazepine.
KetoconazoleKetoconazole may increase the effect of carbamazepine.
LamotrigineLamotrigine may increase the adverse effects of carbamazepine by increasing the concentration of its active metabolite, carbamazepine-epoxide. Carbamazepine may decrease the therapeutic effect of lamotrigine by increasing its metabolism. Lamotrigine doses should be adjusted accordingly. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinue or doses are changed.
LevetiracetamConcomitant therapy may results in additive adverse CNS effects.
LevonorgestrelCarbamazepine may decrease the contraceptive effect of levonorgestrel.
LinagliptinCYP3A4 and p-glycoprotein inducers may decreases levels of linagliptin. Monitor concomitant therapy closely.
LovastatinCarbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of lovastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if carbamazepine is initiated, discontinued or dose changed.
LurasidoneConcomitant therapy with a CYP3A4 inducer will decrease levels of lurasidone. Coadministration with lurasidone is contraindicated.
MestranolThis product may cause a slight decrease of contraceptive effect
MethadoneCarbamazepine may decrease the serum level of methadone. Monitor for changes in the therapeutic and adverse effects of methadone if carbamazepine is initiated, discontinued or dose changed.
MethylphenidateCarbamazepine may decrease the effect of methylphendiate.
MetocurineDecreases the effect of muscle relaxant
MetronidazoleMetronidazole increases the effect of carbamazepine
MidazolamCarbamazepine may decrease the effect of the benzodiazepine, midazolam.
MivacuriumDecrease the effect of muscle relaxant
NefazodoneNefazodone increases the effect of carbamazepine
NorethindroneThis product may cause a slight decrease of contraceptive effect
NortriptylineCarbamazepine may decrease the serum concentration of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if carbamazepine is initiated, discontinued or dose changed.
OxtriphyllineCarbamazepine may decrease the serum concentration of oxtriphylline. Oxtriphylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.
OxybutyninOxybutynin may cause carbamazepine toxicity
PancuroniumDecreases the effect of muscle relaxant
PazopanibAffects CYP3A4 metabolism therefore will decrease levels or effect of pazopanib. Consider alternate therapy.
PonatinibStrong CYP3A4 inducers may decrease levels of ponatinib. Monitor concomitant therapy closely.
PonatinibStrong CYP3A4 inducers may decrease levels of ponatinib. Monitor concomitant therapy closely.
PraziquantelMarkedly lower praziquantel levels
QuinupristinThis combination presents an increased risk of toxicity
RegorafenibStrong CYP3A4 inducers may decrease levels of regorafenib.
RilpivirineStrong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
RisperidoneDecreases the effect of risperidone
RitonavirRitonavir increases the effect of carbamazepine
RoflumilastAffects CYP3A4 metabolism, decreases level or effect of roflumilast. Also decreases the level or effect of roflumilast by affecting CYP1A2 metabolism.
RufinamideDecrease concentration of rufinamide thus monitor therapy
SertralineSertraline increases the effect of carbamazepine
SimvastatinCarbamazepine, a p-glycoprotein inducer, may decrease the effect of simvastatin by increasing its efflux. Monitor for changes in the therapeutic and adverse effects of simvastatin if carbamazepine is initiated, discontinued or dose changed.
SunitinibPossible decrease in sunitinib levels
TacrolimusCarbamazepine may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Carbamazepine therapy is initiated, discontinued or altered.
TelithromycinCo-administration may cause decreased Telithromycin and increased Carbemazepine plasma concentrations. Consider alternate therapy.
TemsirolimusCarbamazepine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
TheophyllineCarbamazepine may decrease the serum concentration of theophylline. Theophylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.
TiclopidineTiclopidine increases the effect of carbamazepine
TipranavirConcomitant use may result in decreased Tipranavir and increased Carbamazepine concentrations.
TolvaptanCarbamazepine is a CYP3A4 inducer and will decrease serum concentrations of tolvaptan and ultimately, its clinical effects.
TopiramateCarbamazepine may decrease the effectiveness of Topiramate by increase its clearance. Monitor for changes in the therapeutic and adverse effects of Topiramate if Carbamazepine is initiated, discontinued or dose changed. Adverse effects related to CNS depression have also been observed during concomitant therapy.
TramadolCarbamazepine may decrease the effect of tramadol by increasing Tramadol metabolism and clearance.
TrazodoneThe CYP3A4 inducer, Carbamazepine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Carbamazepine is initiated, discontinued or dose changed.
TretinoinThe strong CYP2C8 inducer, Carbamazepine, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Carbamazepine is initiated, discontinued or dose changed.
TriprolidineThe CNS depressants, Triprolidine and Carbamazepine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
TroleandomycinThe macrolide, troleandomycin, may increase the effect of carbamazepine.
TubocurarineDecreases the effect of muscle relaxant
UlipristalConcomitant therapy with strong CYP3A4 inducers may decrease plasma concentrations of ulipristal and ultimately its effectiveness. Avoid combination therapy.
Valproic AcidDecreases the effect of valproic acid
VandetanibDecreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
VecuroniumDecreases the effect of muscle relaxant
VemurafenibStrong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
VerapamilVerapamil may increase the serum concentration of Carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic/adverse effects of Carbamazepine if Verapamil is initiated, discontinued or dose changed.
VilazodoneCarbamazepine may increase the metabolism of Selective Serotonin Reuptake Inhibitors (SSRI). Specifically those agents metabolized via CYP1A2, 2C, and/or 3A4 isoenzymes. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Carbamazepine. Specifically those SSRIs that inhibit CYP3A4 isoenzymes.
VoriconazoleCarbamazepine may reduce serum concentrations and efficacy of voriconazole likely by increasing its metabolism. Concomitant voriconazole and carbamazepine therapy is contraindicated.
WarfarinCarbamazepine may decrease the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if carbamazepine is initiated, discontinued or dose changed.
ZiprasidoneIncreases the effect and toxicity of ziprasidone
Food Interactions
  • Avoid alcohol.
  • Avoid taking grapefruit or grapefruit juice throughout treatment.
  • Grapefruit can significantly increase serum levels of this product.
  • Take with food, increases availability and reduces irritation.

Targets

1. Sodium channel protein type 5 subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium channel protein type 5 subunit alpha Q14524 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Yang YC, Huang CS, Kuo CC: Lidocaine, carbamazepine, and imipramine have partially overlapping binding sites and additive inhibitory effect on neuronal na+ channels. Anesthesiology. 2010 Jul;113(1):160-74. Pubmed
  4. Yang YC, Kuo CC: Inhibition of Na(+) current by imipramine and related compounds: different binding kinetics as an inactivation stabilizer and as an open channel blocker. Mol Pharmacol. 2002 Nov;62(5):1228-37. Pubmed
  5. Lipkind GM, Fozzard HA: Molecular model of anticonvulsant drug binding to the voltage-gated sodium channel inner pore. Mol Pharmacol. 2010 Oct;78(4):631-8. Epub 2010 Jul 19. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. Pubmed
  2. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. Pubmed
  3. Cazali N, Tran A, Treluyer JM, Rey E, d’Athis P, Vincent J, Pons G: Inhibitory effect of stiripentol on carbamazepine and saquinavir metabolism in human. Br J Clin Pharmacol. 2003 Nov;56(5):526-36. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Cazali N, Tran A, Treluyer JM, Rey E, d’Athis P, Vincent J, Pons G: Inhibitory effect of stiripentol on carbamazepine and saquinavir metabolism in human. Br J Clin Pharmacol. 2003 Nov;56(5):526-36. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

9. UDP-glucuronosyltransferase 2B7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 2B7 P16662 Details

References:

  1. Kim KA, Oh SO, Park PW, Park JY: Effect of probenecid on the pharmacokinetics of carbamazepine in healthy subjects. Eur J Clin Pharmacol. 2005 Jun;61(4):275-80. Epub 2005 May 25. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Geick A, Eichelbaum M, Burk O: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem. 2001 May 4;276(18):14581-7. Epub 2001 Jan 31. Pubmed
  2. Owen A, Pirmohamed M, Tettey JN, Morgan P, Chadwick D, Park BK: Carbamazepine is not a substrate for P-glycoprotein. Br J Clin Pharmacol. 2001 Apr;51(4):345-9. Pubmed
  3. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed
  4. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. Pubmed
  5. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed

2. RalA-binding protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
RalA-binding protein 1 Q15311 Details

References:

  1. Awasthi S, Hallene KL, Fazio V, Singhal SS, Cucullo L, Awasthi YC, Dini G, Janigro D: RLIP76, a non-ABC transporter, and drug resistance in epilepsy. BMC Neurosci. 2005 Sep 27;6:61. Pubmed

3. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Ufer M, Mosyagin I, Muhle H, Jacobsen T, Haenisch S, Hasler R, Faltraco F, Remmler C, von Spiczak S, Kroemer HK, Runge U, Boor R, Stephani U, Cascorbi I: Non-response to antiepileptic pharmacotherapy is associated with the ABCC2 -24C>T polymorphism in young and adult patients with epilepsy. Pharmacogenet Genomics. 2009 May;19(5):353-62. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11