CLEMASTINE FUMARATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H26ClNO.C4H4O4
Molecular Weight	459.962
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.CN1CCC[C@@H]1CCO[C@](C)(C2=CC=CC=C2)C3=CC=C(Cl)C=C3

InChI

InChIKey=PMGQWSIVQFOFOQ-YKVZVUFRSA-N

InChI=1S/C21H26ClNO.C4H4O4/c1-21(17-7-4-3-5-8-17,18-10-12-19(22)13-11-18)24-16-14-20-9-6-15-23(20)2;5-3(6)1-2-4(7)8/h3-5,7-8,10-13,20H,6,9,14-16H2,1-2H3;1-2H,(H,5,6)(H,7,8)/b;2-1+/t20-,21-;/m1./s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00283
Curator's Comment: Description was created based on several sources, including http://www.sciencedirect.com/topics/page/Clemastine and https://www.drugs.com/pro/clemastine.html

Clemastine is an antihistamine with anticholinergic (drying) and sedative side effects. Clemastine is a selective histamine H1 antagonist and binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. It is used for the relief of symptoms associated with allergic rhinitis such as sneezing, rhinorrhea, pruritus and acrimation. Also for the management of mild, uncomplicated allergic skin manifestations of urticaria and angioedema. Used as self-medication for temporary relief of symptoms associated with the common cold.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Trypanosoma cruzi 12 Target ID: CHEMBL368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25033456	Inhibitor 8297	0.4 µM [IC50]
HERG 92 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16288909	Inhibitor 8297	12.0 nM [IC50]
Cytochrome P450 2D6 61 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9616188	Inhibitor 8297	2.0 µM [Ki]
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: http://www.drugbank.ca/drugs/DB00283	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic rhinitis 100 Sources: https://www.drugs.com/pro/clemastine.html	Primary		Approved 8429	CLEMASTINE Approved Use Clemastine fumarate tablets are indicated for the relief of symptoms associated with allergic rhinitis such as sneezing, rhinorrhea, pruritus, and lacrimation. Clemastine fumarate tablets are also indicated for the relief of mild, uncomplicated allergic skin manifestations of urticaria and angioedema. Launch Date 1992
Urticaria 39 Sources: https://www.drugs.com/pro/clemastine.html	Primary		Approved 8429	CLEMASTINE Approved Use Clemastine fumarate tablets are indicated for the relief of symptoms associated with allergic rhinitis such as sneezing, rhinorrhea, pruritus, and lacrimation. Clemastine fumarate tablets are also indicated for the relief of mild, uncomplicated allergic skin manifestations of urticaria and angioedema. Launch Date 1992

C_max

Value	Dose	Analyte	Population
0.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15664345/	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	CLEMASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
650 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:	CLEMASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1010 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	CLEMASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
4.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15664345/	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	CLEMASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
15529 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:	CLEMASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
26230 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	CLEMASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15664345/	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	CLEMASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
17.28 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:	CLEMASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
23.94 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	CLEMASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
4 mg single, oral Highest studied dose Dose: 4 mg Route: oral Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8930778	healthy n = 24 Health Status: healthy Sex: M Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/8930778	Sources: https://pubmed.ncbi.nlm.nih.gov/8930778
0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	Disc. AE: Itching, Rash... AEs leading to discontinuation/dose reduction: Itching (1 patient) Rash (1 patient) Nausea (1 patient) Pallor (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58
1 mg single, oral Dose: 1 mg Route: oral Route: single Dose: 1 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	Disc. AE: Vomiting... AEs leading to discontinuation/dose reduction: Vomiting (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58

AEs

AE	Significance	Dose	Population
Itching	1 patient Disc. AE	0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58
Nausea	1 patient Disc. AE	0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58
Pallor	1 patient Disc. AE	0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58
Rash	1 patient Disc. AE	0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58
Vomiting	1 patient Disc. AE	1 mg single, oral Dose: 1 mg Route: oral Route: single Dose: 1 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9616188/	yes [Ki 2 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/27279987/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/16288909/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3738	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3738
ChemicalBook	CB3376056	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3376056
ZINC	ZINC000000402830	http://zinc15.docking.org/substances/ZINC000000402830

PubMed

Title	Date	PubMed
Dermatopathic lymphadenopathy: a differential diagnosis of enlarged lymph nodes in uremic pruritus.	2006 Dec	17176922
Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia.	2006 Dec	17089107
[Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation].	2006 Nov-Dec	17175917
Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer.	2006 Oct 9	16969354
A novel self-microemulsifying formulation of paclitaxel for oral administration to patients with advanced cancer.	2006 Sep 18	16926835
Development and full validation of a sensitive quantitative assay for the determination of clemastine in human plasma by liquid chromatography-tandem mass spectrometry.	2007 Aug 15	17475437
[Emergency checklist: angioedema].	2007 Aug 2	17849784
Stereoselective synthesis of (-)-hydroxyclemastine as a versatile intermediate for the H1 receptor antagonist clemastine.	2007 Dec	18254238
Early detection of adverse drug events within population-based health networks: application of sequential testing methods.	2007 Dec	17955500
Psoriasis following growth hormone therapy in a child.	2007 Jan	17179190
Influence of immunomodulatory drugs on the cytotoxicity induced by monoclonal antibody 17-1A and interleukin-2.	2007 Mar	17562330
Intraoperative anaphylaxis after intravenous atropine.	2007 Mar	17087843
[Angioneurotic orolingual edema associated with the use of rt-PA following a stroke].	2007 Oct	17694290
Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation: frequency and power dependence.	2008 Apr	18044738
Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).	2008 Aug 22	18721465
Histamine upregulates keratinocyte MMP-9 production via the histamine H1 receptor.	2008 Dec	18548114
[Chikungunya: fever and joint pains after vacation in a tropical area].	2008 Feb	18288627
A highly active and tolerable neoadjuvant regimen combining paclitaxel, carboplatin, 5-FU, and radiation therapy in patients with stage II and III esophageal cancer.	2008 Jan	17896144
Spectrophotometric determination of some histamine H1-antagonists drugs in their pharmaceutical preparations.	2008 Jan	17553739
Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response.	2008 Jul	17965121
NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial).	2008 Jul 31	18671847
Major determinants and long-term outcomes of successful balloon dilatation for the pediatric patients with isolated native valvular pulmonary stenosis: a 10-year institutional experience.	2008 Jun 30	18581591
Antagonist affinity measurements at the Gi-coupled human histamine H3 receptor expressed in CHO cells.	2008 Jun 6	18538007
Medication with antihistamines impairs allergen-specific immunotherapy in mice.	2008 Mar	18081882
Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes.	2008 May	18265982
Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS).	2008 Nov 26	19036143
Canine African trypanosoma.	2008 Sep	18811787
Evaluation of efficacy and sedative profiles of H(1) antihistamines by large-scale surveillance using the visual analogue scale (VAS).	2008 Sep	18566547
A similarity search using molecular topological graphs.	2009	20037730
Clinical practice. Diagnosis and treatment of cow's milk allergy.	2009 Aug	19271238
Application of prolonged microdialysis sampling in carboplatin-treated cancer patients.	2009 Aug	19096847
Ebastine in the light of CONGA recommendations for the development of third-generation antihistamines.	2009 Aug 31	21437146
Acute cough: a diagnostic and therapeutic challenge.	2009 Dec 16	20015366
Psoriasis vulgaris and digestive system disorders: is there a linkage?	2009 Jan	20164041
[Documentation for acute treatment with clemastine (Tavegyl) is missing].	2009 Jul 22-Aug 4	19739446
Psychoactive medication and traffic safety.	2009 Mar	19440432
Hypersensitivity reactions associated with platinum antineoplastic agents: a systematic review.	2010	20886011
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
Diagnostic approach identifying hydroxyethyl starch (HES) triggering a severe anaphylactic reaction during anesthesia in a 15-year-old boy.	2010 Dec	20556705
Use of venlafaxine compared with other antidepressants and the risk of sudden cardiac death or near death: a nested case-control study.	2010 Feb 5	20139216
Hyperimmune anti-HBs plasma as alternative to commercial immunoglobulins for prevention of HBV recurrence after liver transplantation.	2010 Jul 4	20598161
Anaphylaxis to mefenamic acid in a patient with new onset of systemic lupus erythematosus.	2010 Jul-Aug	20153574
[Discriminant function analysis in the assessment of laboratory test data in the correction of traditional therapy for mild icteric form of viral hepatitis B in children with food allergy].	2010 Jun	20734860
Chloroquine-induced Pruritus.	2010 May	21188034
Synthesis of (-)-(S,S)-clemastine by invertive N --> C aryl migration in a lithiated carbamate.	2010 May 21	20405879
Structural elucidation of N-oxidized clemastine metabolites by liquid chromatography/tandem mass spectrometry and the use of Cunninghamella elegans to facilitate drug metabolite identification.	2010 May 30	20411584
Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT) in combination with cetuximab and chemotherapy: the REACH protocol.	2010 Nov 26	21108850
[Progress of study on antitumor effects of antibody dependent cell mediated cytotoxicity--review].	2010 Oct	21129296
A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours.	2010 Oct 26	20877350
Therapeutic efficacy of icatibant in angioedema induced by angiotensin-converting enzyme inhibitors: a case series.	2010 Sep	20447725

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Allergic Rhinitis Initial dose: 1.34 mg orally twice a day. Dosage may be increased as required, but not to exceed 2.68 mg orally 3 times a day.

Route of Administration: Oral

In Vitro Use Guide

IHERG tails at -40 mV following depolarizing pulses to +20 mV were inhibited by clemastine with an IC50 value of 12 nM in HEK 293 cells

Name

Type

Language

CLEMASTINE FUMARATE

Official Name

English

Clemastine fumarate [WHO-DD]

Common Name

English

TAVIST

Brand Name

English

CLEMASTINE FUMARATE [MART.]

Common Name

English

CLEMASTINE FUMARATE [HSDB]

Common Name

English

CLEMASTINE FUMARATE [ORANGE BOOK]

Common Name

English

CLEMASTINE FUMARATE [USP MONOGRAPH]

Common Name

English

CLEMASTINE FUMARATE [VANDF]

Common Name

English

CLEMASTINE FUMARATE [EP MONOGRAPH]

Common Name

English

CLEMASTINE FUMARATE [JAN]

Common Name

English

CLEMASTINE FUMARATE COMPONENT OF TAVIST-D

Common Name

English

TAVIST-D COMPONENT CLEMASTINE FUMARATE

Common Name

English

PYRROLIDINE, 2-(2-(1-(4-CHLOROPHENYL)-1-PHENYLETHOXY)ETHYL)-1-METHYL-, (R-(R*,R*))-, (E)-2-BUTENEDIOATE (1:1)

Common Name

English

CLEMASTINE FUMARATE [USP-RS]

Common Name

English

CLEMASTINE HYDROGEN FUMARATE [MI]

Common Name

English

CLEMASTINE HYDROGEN FUMARATE

Common Name

English

(+)-(2R)-2-(2-(((R)-P-CHLORO-.ALPHA.-METHYL-.ALPHA.-PHENYLBENZYL)OXY)ETHYL)-1-METHYLPYRROLIDINE FUMARATE (1:1)

Common Name

English

CLEMASTINE FUMARATE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578