Ketotifen

Identification

Name
Ketotifen
Accession Number
DB00920
Description

A cycloheptathiophene blocker of histamine H1 receptors and release of inflammatory mediators. It has been proposed for the treatment of asthma, rhinitis, skin allergies, and anaphylaxis.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 309.425
Monoisotopic: 309.118734925
Chemical Formula
C19H19NOS
Synonyms
  • Ketotifen
  • Ketotifene
  • Ketotifeno
  • Ketotifenum

Pharmacology

Indication

Indicated as an add-on or prophylactic oral medication in the chronic treatment of mild atopic asthmatic children. Also used as self-medication for the temporary relief of itching of the eye due to allergic conjunctivitis (ophthalmic).

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Ketotifen is a fast acting non-competitive histamine antagonist. It inhibits the release of mediators from mast cells. It is a non-bronchodilator antiasthmatic drug (when taken orally).

Mechanism of action

Ketotifen is a relatively selective, non-competitive histamine antagonist (H1-receptor) and mast cell stabilizer. Ketotifen inhibits the release of mediators from mast cells involved in hypersensitivity reactions. Decreased chemotaxis and activation of eosinophils have also been demonstrated. Ketotifen also inhibits cAMP phosphodiesterase. Properties of ketotifen which may contribute to its antiallergic activity and its ability to affect the underlying pathology of asthma include inhibition of the development of airway hyper-reactivity associated with activation of platelets by PAF (Platelet Activating Factor), inhibition of PAF-induced accumulation of eosinophils and platelets in the airways, suppression of the priming of eosinophils by human recombinant cytokines and antagonism of bronchoconstriction due to leukotrienes. Ketotifen inhibits of the release of allergic mediators such as histamine, leukotrienes C4 and D4(SRS-A) and PAF.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Humans
U6-phosphogluconate dehydrogenase, decarboxylating
inhibitor
Humans
Absorption

Following oral administration absorption is at least 60%

Volume of distribution
Not Available
Protein binding

75%

Metabolism

Primarily hepatic. The main metabolite found in both plasma and urine is the inactive ketotifen-N-glucuronide. Nor-ketotifen, the N-demethylated metabolite, and the 10-alpha-hydroxyl derivative are the only other metabolites detectable in human urine.

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Route of elimination
Not Available
Half-life

21 hours (for elimination)

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Adverse reactions include headaches, conjunctival injection and rhinitis.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Ketotifen H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololThe risk or severity of QTc prolongation can be increased when Ketotifen is combined with Acebutolol.
AcrivastineThe risk or severity of QTc prolongation can be increased when Ketotifen is combined with Acrivastine.
AdenosineThe risk or severity of QTc prolongation can be increased when Ketotifen is combined with Adenosine.
AjmalineThe risk or severity of QTc prolongation can be increased when Ketotifen is combined with Ajmaline.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Ketotifen.
AlimemazineThe risk or severity of QTc prolongation can be increased when Ketotifen is combined with Alimemazine.
AmantadineThe risk or severity of QTc prolongation can be increased when Amantadine is combined with Ketotifen.
AmifampridineThe risk or severity of QTc prolongation can be increased when Ketotifen is combined with Amifampridine.
AmiodaroneThe risk or severity of QTc prolongation can be increased when Ketotifen is combined with Amiodarone.
AmisulprideThe risk or severity of QTc prolongation can be increased when Ketotifen is combined with Amisulpride.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

Product Ingredients
IngredientUNIICASInChI Key
Ketotifen fumarateHBD503WORO34580-14-8YNQQEYBLVYAWNX-WLHGVMLRSA-N
International/Other Brands
Totifen (Patron) / Zasten (Novartis)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ketotifen Ophthalmic SolutionSolutionOphthalmicSterimax Inc2013-03-07Not applicableCanada flag
ZaditenTabletOralTEVA Canada Limited1990-12-31Not applicableCanada flag
ZaditenSyrupOralTEVA Canada Limited1990-12-31Not applicableCanada flag
Zaditen - Dps 1mg/mlSolution / dropsOralNovartisNot applicableNot applicableCanada flag
ZaditorSolution0.25 mgOphthalmicLaboratoires Thea2000-08-01Not applicableCanada flag
ZaditorSolution0.345 mg/1mLOphthalmicNovartis Ophthalmics1999-07-022008-10-31US flag
ZaditorSolution0.25 mgOphthalmicNovartis2006-08-032012-01-17Canada flag
ZaditorSolution0.345 mg/1mLOphthalmicPhysicians Total Care, Inc.2002-11-042010-12-29US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-ketotifen - Syr 1mg/5mlSyrupOralApotex Corporation1996-11-072019-01-16Canada flag
Jamp-ketotifenSolutionOphthalmicJamp Pharma CorporationNot applicableNot applicableCanada flag
Novo-ketotifen - Syr 1mg/5mlSyrupOralNovopharm Limited1995-12-312015-10-26Canada flag
Novo-ketotifen Tab 1mgTabletOralNovopharm Limited1997-07-292013-02-11Canada flag
Nu-ketotifen Syrup - 1mg/5mlSyrupOralNu Pharm Inc1996-12-092012-09-04Canada flag
PMS-ketotifenSyrupOralPharmascience Inc1998-08-312013-02-07Canada flag
PMS-ketotifenTabletOralPharmascience Inc1998-08-312013-02-07Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AlawaySolution / drops0.25 mg/1mLOphthalmicBausch & Lomb Incorporated2006-12-01Not applicableUS flag
Alaway Preservative FreeSolution / drops0.35 mg/1mLOphthalmicBausch & Lomb Incorporated2020-09-24Not applicableUS flag
Allergy EyeSolution / drops0.25 mg/1mLOphthalmicCVS Health2011-01-072014-07-01US flag
Allergy EyeSolution / drops0.25 mg/1mLOphthalmicH.E.B.2010-09-152015-05-01US flag
Allergy Eye DropsSolution / drops0.35 mg/1mLOphthalmicAdvanced Vision Research (Subsidiary of Akorn, Inc.)2013-11-14Not applicableUS flag
Allergy Eye DropsSolution / drops0.35 mg/1mLOphthalmicH E B2014-02-25Not applicableUS flag
Allergy Eye DropsSolution / drops0.35 mg/1mLOphthalmicCardinal Health2014-01-132016-07-01US flag
Allergy Eye Original Prescription StrengthSolution / drops0.25 mg/1mLOphthalmicMeijer Distribution1995-12-122015-01-01US flag
Allergy Relief EyeSolution / drops0.25 mg/1mLOphthalmicWestern Family Foods2011-05-252015-06-01US flag
Allergy Relief Eye DropsSolution / drops0.35 mg/1mLOphthalmicKinray Inc.2014-03-182016-09-01US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AlawayKetotifen fumarate (0.25 mg/1mL) + Ketotifen fumarate (0.25 mg/1mL)OphthalmicBausch & Lomb Incorporated2006-12-012015-09-30US flag
AlawayKetotifen fumarate (0.25 mg/1mL) + Ketotifen fumarate (0.25 mg/1mL)OphthalmicBausch & Lomb Incorporated2006-12-012015-09-30US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ZaditorKetotifen fumarate (0.345 mg/1mL)SolutionOphthalmicPhysicians Total Care, Inc.2002-11-042010-12-29US flag

Categories

ATC Codes
S01GX08 — KetotifenR06AX17 — Ketotifen
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as cycloheptathiophenes. These are polycyclic compounds containing a thiophene ring fused to a 7 member carbocyclic moiety. Thiophene is 5-membered ring consisting of four carbon atoms and one sulfur atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Cycloheptathiophenes
Sub Class
Not Available
Direct Parent
Cycloheptathiophenes
Alternative Parents
Aryl alkyl ketones / Piperidines / Benzenoids / Thiophenes / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Amine / Aromatic heteropolycyclic compound / Aryl alkyl ketone / Aryl ketone / Azacycle / Benzenoid / Cycloheptathiophene / Heteroaromatic compound / Hydrocarbon derivative / Ketone
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
X49220T18G
CAS number
34580-13-7
InChI Key
ZCVMWBYGMWKGHF-UHFFFAOYSA-N
InChI
InChI=1S/C19H19NOS/c1-20-9-6-13(7-10-20)18-15-5-3-2-4-14(15)12-17(21)19-16(18)8-11-22-19/h2-5,8,11H,6-7,9-10,12H2,1H3
IUPAC Name
2-(1-methylpiperidin-4-ylidene)-6-thiatricyclo[8.4.0.0³,⁷]tetradeca-1(14),3(7),4,10,12-pentaen-8-one
SMILES
CN1CCC(CC1)=C1C2=C(SC=C2)C(=O)CC2=CC=CC=C12

References

Synthesis Reference

Roy W. Bryant, Ravi Parihar, Thomas Rowe, Susan Caballa, "Methods of Making and Using Stable Pharmaceutical Compositions Comprising Ketotifen and Naphazoline." U.S. Patent US20110312998, issued December 22, 2011.

US20110312998
General References
Not Available
Human Metabolome Database
HMDB0015056
KEGG Drug
D01332
PubChem Compound
3827
PubChem Substance
46508921
ChemSpider
3695
BindingDB
94597
RxNav
6146
ChEBI
92511
ChEMBL
CHEMBL534
ZINC
ZINC000000004351
Therapeutic Targets Database
DAP000329
PharmGKB
PA450152
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ketotifen
AHFS Codes
  • 52:02.00 — Antiallergic Agents
  • 04:00.00 — Antihistamine Drugs
  • 04:92.00 — Other Antihistamines
FDA label
Download (9.05 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAsthma1
4CompletedTreatmentConjunctivitis, Seasonal Allergic1
4Unknown StatusTreatmentDengue Fever / Pleural Effusions1
3CompletedNot AvailableConjunctivitis, Seasonal Allergic1
3CompletedBasic ScienceFibromyalgia1
3CompletedTreatmentAtopic Dermatitis (AD)1
3CompletedTreatmentAtopy / Skin Inflammation1
3CompletedTreatmentConjunctivitis, Seasonal Allergic5
3CompletedTreatmentRhinitis, Allergic, Perennial2
3CompletedTreatmentVernal Keratoconjunctivitis1

Pharmacoeconomics

Manufacturers
  • Bausch and lomb inc
  • Akorn inc
  • Alcon inc
  • Apotex inc etobicoke site
  • Novartis pharmaceuticals corp
Packagers
  • Akorn Inc.
  • Allergan Inc.
  • Apotex Inc.
  • Bausch & Lomb Inc.
  • Ciba Vision Canada Inc.
  • Novartis AG
  • Physicians Total Care Inc.
  • Spectrum Pharmaceuticals
Dosage Forms
FormRouteStrength
Solution / dropsOphthalmic0.35 mg/1mL
Syrup100 ml
SyrupOral
Tablet
Syrup1 MG/5ML
Tablet, extended releaseOral2 MG
Solution / dropsOphthalmic0.025 %
SolutionOphthalmic0.25 g/1mL
SolutionOphthalmic0.25 mg/1mL
SolutionOphthalmic0.25 mg
SolutionConjunctival; Ophthalmic0.5 mg
SolutionOral27.6 mg
CapsuleOral1 mg
SolutionConjunctival; Ophthalmic0.25 mg
Capsule1 mg
SolutionOphthalmic0.35 mg/1mL
SolutionOphthalmic
Solution / dropsOphthalmic250 Mikrogramm/ml
TabletOral1 mg
SolutionOral20 mg
SyrupOral0.02 g
SyrupOral20 mg
SyrupOral0.0275 g
SolutionOphthalmic0.5 mg
Solution / dropsOphthalmic0.345 mg/1mL
Tablet1 mg
Solution / dropsOphthalmic0.1 mg/mL
Solution / dropsOral2 MG/ML
Tablet, soluble1 MG
Tablet, coatedOral1 mg
SolutionOphthalmic.25 mg/1mL
Solution / dropsOphthalmic25 mcg/1mL
Solution / dropsOphthalmic25 mg/100mL
SyrupOral0.2 MG/ML
TabletOral
Solution / dropsOral
Solution / dropsOphthalmic0.25 mg/ml
Solution / dropsOral1 mg/ml
Tablet2 mg
SolutionOphthalmic.35 mg/1mL
SolutionOphthalmic0.345 mg/1mL
Solution / dropsOphthalmic0.25 mg/1mL
Prices
Unit descriptionCostUnit
Ketotifen fumarate powder926.63USD g
Zaditor 0.025% Solution 5ml Bottle74.96USD bottle
Ketotifen fum 0.025% eye drops2.44USD ml
Refresh 0.025% eye drops2.2USD ml
Zaditor 0.025% eye drops2.15USD ml
Alaway 0.025% eye drops0.96USD ml
Zaditen 1 mg Tablet0.83USD tablet
Novo-Ketotifen 1 mg Tablet0.66USD tablet
Novo-Ketotifen 0.2 mg/ml Syrup0.14USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)152-153U.S. Patents 3,682,930; 3,770,728; and 3,960,894
logP2.2Not Available
pKa8.43Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00787 mg/mLALOGPS
logP3.49ALOGPS
logP3.35ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)12.3ChemAxon
pKa (Strongest Basic)7.15ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area20.31 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity101.73 m3·mol-1ChemAxon
Polarizability34.61 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9923
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.87
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IINon-inhibitor0.7474
Renal organic cation transporterInhibitor0.8198
CYP450 2C9 substrateNon-substrate0.7542
CYP450 2D6 substrateNon-substrate0.5638
CYP450 3A4 substrateSubstrate0.6984
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8607
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6414
Ames testNon AMES toxic0.7576
CarcinogenicityNon-carcinogens0.9649
BiodegradationNot ready biodegradable0.9547
Rat acute toxicity2.7979 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6336
hERG inhibition (predictor II)Non-inhibitor0.5145
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Details
1. Histamine H1 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Mita H, Shida T: Comparison of anti-allergic activities of the histamine H1 receptor antagonists epinastine, ketotifen and oxatomide in human leukocytes. Arzneimittelforschung. 1995 Jan;45(1):36-40. [PubMed:7893266]
  2. Okabe S, Nakaji S, Tachibana M: Effect of ketotifen on acute gastric lesions and gastric secretion in rats. Jpn J Pharmacol. 1992 Jun;59(2):251-4. [PubMed:1434122]
  3. Hashimoto T, Ohata H, Honda K: Lysophosphatidic acid (LPA) induces plasma exudation and histamine release in mice via LPA receptors. J Pharmacol Sci. 2006 Jan;100(1):82-7. Epub 2006 Jan 11. [PubMed:16404130]
  4. Ito K, Sakamoto T, Hayashi Y, Morishita M, Shibata E, Sakai K, Takeuchi Y, Torii S: Role of tachykinin and bradykinin receptors and mast cells in gaseous formaldehyde-induced airway microvascular leakage in rats. Eur J Pharmacol. 1996 Jul 4;307(3):291-8. [PubMed:8836617]
  5. Yokoyama H, Iinuma K, Yanai K, Watanabe T, Sakurai E, Onodera K: Proconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography. Methods Find Exp Clin Pharmacol. 1993 Apr;15(3):183-8. [PubMed:8101246]
  6. Werner-Klein M, Goggel R, Westhof A, Erb KJ: Development and characterisation of a novel and rapid lung eosinophil influx model in the rat. Pulm Pharmacol Ther. 2008 Aug;21(4):648-56. doi: 10.1016/j.pupt.2008.03.002. Epub 2008 Apr 7. [PubMed:18490184]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phosphogluconate dehydrogenase (decarboxylating) activity
Specific Function
Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
Gene Name
PGD
Uniprot ID
P52209
Uniprot Name
6-phosphogluconate dehydrogenase, decarboxylating
Molecular Weight
53139.56 Da
References
  1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Aug;25(4):476-9. doi: 10.3109/14756360903257900. [PubMed:20235752]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2020 01:55

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