U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C15H12N2O.2H2O
Molecular Weight 272.2997
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARBAMAZEPINE DIHYDRATE

SMILES

c1ccc2c(c1)C=Cc3ccccc3N2C(=N)O.O.O

InChI

InChIKey=UPTJXAHTRRBMJE-UHFFFAOYSA-N
InChI=1S/C15H12N2O.2H2O/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);2*1H2

HIDE SMILES / InChI

Molecular Formula C15H12N2O
Molecular Weight 236.2691
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including: https://www.drugs.com/carbamazepine.html http://www.rxlist.com/carnexiv-drug.htm http://www.wikidoc.org/index.php/Carbamazepine

Carbamazepine is an analgesic, anti-epileptic agent that is FDA approved for the treatment of epilepsy, trigeminal neuralgia. It appears to act by reducing polysynaptic responses and blocking the post-tetanic potentiation. It depresses thalamic potential and bulbar and polysynaptic reflexes, including the linguomandibular reflex in cats. Commonly reported side effects of carbamazepine include: dizziness, drowsiness, nausea, ataxia, and vomiting. Carbamazepine is a potent inducer of hepatic CYP1A2, 2B6, 2C9/19, and 3A4 and may reduce plasma concentrations of concomitant medications mainly metabolized by CYP1A2, 2B6, 2C9/19, and 3A4 through induction of their metabolism, like Boceprevir, Cyclophosphamide, Aripiprazole, Tacrolimus, Temsirolimus and others.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
152.0 µM [IC50]
25.0 µM [Ki]
Target ID: Q9NY46|||Q9Y6P4
Gene ID: 6328.0
Gene Symbol: SCN3A
Target Organism: Homo sapiens (Human)
16.0 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TEGRETOL

Approved Use

Epilepsy Carbamazepine is indicated for use as an anticonvulsant drug. Evidence supporting efficacy of carbamazepine as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types: 1. Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these seizures appear to show greater improvement than those with other types. 2. Generalized tonic-clonic seizures (grand mal). 3. Mixed seizure patterns which include the above, or other partial or generalized seizures. Absence seizures (petit mal) do not appear to be controlled by carbamazepine (see PRECAUTIONS, General). Trigeminal Neuralgia Carbamazepine is indicated in the treatment of the pain associated with true trigeminal neuralgia. Beneficial results have also been reported in glossopharyngeal neuralgia. This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains.

Launch Date

-5.7110401E10
Primary
TEGRETOL

Approved Use

Epilepsy Carbamazepine is indicated for use as an anticonvulsant drug. Evidence supporting efficacy of carbamazepine as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types: 1. Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these seizures appear to show greater improvement than those with other types. 2. Generalized tonic-clonic seizures (grand mal). 3. Mixed seizure patterns which include the above, or other partial or generalized seizures. Absence seizures (petit mal) do not appear to be controlled by carbamazepine (see PRECAUTIONS, General). Trigeminal Neuralgia Carbamazepine is indicated in the treatment of the pain associated with true trigeminal neuralgia. Beneficial results have also been reported in glossopharyngeal neuralgia. This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains.

Launch Date

-5.7110401E10
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.2 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: FASTED
1.9 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
11 μg/mL
800 mg 2 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
4.3 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: HIGH-FAT
3.2 μg/mL
1600 mg 1 times / day multiple, oral
dose: 1600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
1.5 μg/mL
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
0.11 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
2.2 μg/mL
800 mg 2 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
32.6 μg × h/mL
1600 mg 1 times / day multiple, oral
dose: 1600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
15.7 μg × h/mL
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
37.5 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
14.5 h
800 mg 2 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
34 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
24%
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
50%
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources: Page: p.1297
unhealthy, 73.1 ± 5.5
n = 91
Health Status: unhealthy
Condition: Epilepsy
Age Group: 73.1 ± 5.5
Sex: M+F
Population Size: 91
Sources: Page: p.1297
Disc. AE: Skin and subcutaneous conditions NEC, Fatigue...
AEs leading to
discontinuation/dose reduction:
Skin and subcutaneous conditions NEC (8.8%)
Fatigue
Somnolence
Sources: Page: p.1297
AEs

AEs

AESignificanceDosePopulation
Skin and subcutaneous conditions NEC 8.8%
Disc. AE
1000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources: Page: p.1297
unhealthy, 73.1 ± 5.5
n = 91
Health Status: unhealthy
Condition: Epilepsy
Age Group: 73.1 ± 5.5
Sex: M+F
Population Size: 91
Sources: Page: p.1297
Fatigue Disc. AE
1000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources: Page: p.1297
unhealthy, 73.1 ± 5.5
n = 91
Health Status: unhealthy
Condition: Epilepsy
Age Group: 73.1 ± 5.5
Sex: M+F
Population Size: 91
Sources: Page: p.1297
Somnolence Disc. AE
1000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources: Page: p.1297
unhealthy, 73.1 ± 5.5
n = 91
Health Status: unhealthy
Condition: Epilepsy
Age Group: 73.1 ± 5.5
Sex: M+F
Population Size: 91
Sources: Page: p.1297
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
strong
yes (co-administration study)
Comment: Midazolam plasma concentrations reduced dramatically in patients treated with carbamazepine and phenytoin; The CYP3A4-mediated metabolism of cyclosporin is markedly accelerated by carbamazepine comedication; Many other likely DDIs with carbamazepine. See https://pubmed.ncbi.nlm.nih.gov/8877250/
Page: 12.0
yes
yes
yes
yes
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Carbamazepine-associated severe left ventricular dysfunction.
2000
Worsening of symptoms of multiple sclerosis associated with carbamazepine.
2000 Apr 22
Increased seizures after discontinuing carbamazepine: results from the gabapentin monotherapy trial.
2000 Dec
Potential interaction between ritonavir and carbamazepine.
2000 Jul
Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds.
2000 Jul 28
Color vision in epilepsy patients treated with vigabatrin or carbamazepine monotherapy.
2000 May
New developments in the pharmacotherapy of alcohol dependence.
2001
Update on anticonvulsants for the treatment of alcohol withdrawal.
2001
Investigation and medical management of trigeminal neuralgia by consultant oral and maxillofacial surgeons in the British Isles.
2001 Apr
Novel treatments for bipolar disorder.
2001 Apr
Comparison the cognitive effect of anti-epileptic drugs in seizure-free children with epilepsy before and after drug withdrawal.
2001 Apr
Mood and behavioural disorders following traumatic brain injury: clinical evaluation and pharmacological management.
2001 Feb
Determination of the antiepileptics vigabatrin and gabapentin in dosage forms and biological fluids using Hantzsch reaction.
2001 Feb
Illness characteristics and their association with prescription patterns for bipolar I disorder.
2001 Feb
Population pharmacokinetic modeling of steady state carbamazepine clearance in children, adolescents, and adults.
2001 Feb
Recommendations for the management of behavioral and psychological symptoms of dementia.
2001 Feb
Anticonvulsant and sodium channel blocking activity of higher doses of clenbuterol.
2001 Feb
The influence of food on the bioavailability of a twice-daily controlled release carbamazepine formulation.
2001 Feb
Relation between dosage of carbamazepine and concentration in hair and plasma samples from a compliant inpatient epileptic population.
2001 Feb
Adverse drug interaction between risperidone and carbamazepine in a patient with chronic schizophrenia and deficient CYP2D6 activity.
2001 Feb
Pleomorphic xanthoastrocytoma: report of a case diagnosed by intraoperative cytopathological examination.
2001 Feb
Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy.
2001 Feb
Significance of atypical presentation of symptomatic SUNCT: a case report.
2001 Feb
The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study.
2001 Feb
Independent short-term variability of spike-like (600 Hz) and postsynaptic (N20) cerebral SEP components.
2001 Feb 12
A model of atypical absence seizures: EEG, pharmacology, and developmental characterization.
2001 Feb 13
[Febrile convulsions, Treatment and prognosis].
2001 Feb 19
Determination of drug residues in water by the combination of liquid chromatography or capillary electrophoresis with electrospray mass spectrometry.
2001 Feb 23
Seizures in multiple sclerosis.
2001 Jan
Carbamazepine hypersensitivity syndrome mimicking mycosis fungoides.
2001 Jan
Relief of cluster headache and cranial neuralgias. Promising prophylactic and symptomatic treatments.
2001 Jan
Ritonavir-induced carbamazepine toxicity.
2001 Jan
Acute intermittent porphyria, seizures, and antiepileptic drugs: a report on a 3-year-old Nigerian boy.
2001 Jan
Effects of antiepileptic drugs on rat platelet aggregation: ex vivo and in vitro study.
2001 Jan
Additional educational needs in children born to mothers with epilepsy.
2001 Jan
[Klüver-Bucy syndrome in herpetic meningoencephalitis].
2001 Jan 27
Changes in color vision after a single dose of vigabatrin or carbamazepine in healthy volunteers.
2001 Jan-Feb
Mood stabilizers and ion regulation.
2001 Jan-Feb
Taking the sting out of trigeminal neuralgia.
2001 Mar
Effects of antimanic mood-stabilizing drugs on fetuses, neonates, and nursing infants.
2001 Mar
Influence of retigabine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice.
2001 Mar
Treatment of bipolar affective disorder in clinical practice.
2001 Mar
Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms.
2001 Mar
Mood-stabilisers reduce the risk of developing antidepressant-induced maniform states in acute treatment of bipolar I depressed patients.
2001 Mar
Suppressive effects of oxcarbazepine on tooth pulp-evoked potentials recorded at the trigeminal spinal tract nucleus in cats.
2001 Mar
The effects of terpene enhancers on the percutaneous permeation of drugs with different lipophilicities.
2001 Mar 14
Carbamazepine prevents imipramine-induced behavioural sensitization to the dopamine D(2)-like receptor agonist quinpirole.
2001 Mar 23
Separation of olanzapine, carbamazepine and their main metabolites by capillary electrophoresis with pseudo-stationary phases.
2001 Mar 5
Rapid loss of insulin secretion in a patient with fulminant type 1 diabetes mellitus and carbamazepine hypersensitivity syndrome.
2001 Mar 7
New anticonvulsants for use in pediatric patients (part I).
2001 Mar-Apr
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: The total daily dose of CARNEXIV is 70% of the total daily oral carbamazepine dose from which patients are being switched. The total daily dose of CARNEXIV should be equally divided in four 30-minute infusions, separated by 6 hours.
Initial Dose: 400 mg per day. Subsequent Dose: add up to 200 mg per day at weekly intervals. Maximum daily dose is 1600 mg
Route of Administration: Other
Human liver microsomes (HLMs) converted carbamazepine (30-300 microM) to 3-hydroxycarbamazepine at rates >25 times those of 2-hydroxycarbamazepine. Rates of carbamazepine 2- and 3-hydroxylation correlated strongly with CYP2B6 activity (r >or= 0.757) in a panel of HLMs (n = 8). Carbamazepine 3-hydroxylation also correlated significantly with CYP2C8 activity at a carbamazepine concentration of 30 microM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 02:15:23 UTC 2021
Edited
by admin
on Sat Jun 26 02:15:23 UTC 2021
Record UNII
78M1RMW7Q8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CARBAMAZEPINE DIHYDRATE
Common Name English
5H-DIBENZ(B,F)AZEPINE-5-CARBOXAMIDE, HYDRATE (1:2)
Systematic Name English
Code System Code Type Description
PUBCHEM
158856
Created by admin on Sat Jun 26 02:15:23 UTC 2021 , Edited by admin on Sat Jun 26 02:15:23 UTC 2021
PRIMARY
CAS
85756-57-6
Created by admin on Sat Jun 26 02:15:23 UTC 2021 , Edited by admin on Sat Jun 26 02:15:23 UTC 2021
PRIMARY
EPA CompTox
85756-57-6
Created by admin on Sat Jun 26 02:15:23 UTC 2021 , Edited by admin on Sat Jun 26 02:15:23 UTC 2021
PRIMARY
FDA UNII
78M1RMW7Q8
Created by admin on Sat Jun 26 02:15:23 UTC 2021 , Edited by admin on Sat Jun 26 02:15:23 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE