Alcaftadine

Identification

Summary

Alcaftadine is a H1 histamine receptor antagonist for ophthalmic use to prevent itching associated with allergic conjunctivitis.

Brand Names
Lastacaft
Generic Name
Alcaftadine
DrugBank Accession Number
DB06766
Background

Alcaftadine is a H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. This drug was approved in July 2010.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 307.3895
Monoisotopic: 307.168462309
Chemical Formula
C19H21N3O
Synonyms
  • Alcaftadina
  • Alcaftadine
  • Alcaftadinum
External IDs
  • R 89674
  • R-89674
  • R89674

Pharmacology

Indication

For the prevention of itching associated with allergic conjunctivitis.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Following bilateral topical ocular administration of alcaftadine ophthalmic solution, 0.25%, the mean plasma Cmax of alcaftadine was approximately 60 pg/mL and the median Tmax occurred at 15 minutes. Plasma concentrations of alcaftadine were below the lower limit of quantification (10 pg/mL) by 3 hours after dosing. The mean Cmax of the active carboxylic acid metabolite was approximately 3 ng/mL and occurred at 1 hour after dosing. Plasma concentrations of the carboxylic acid metabolite were below the lower limit of quantification (100 pg/mL) by 12 hours after dosing.

Mechanism of action

Alcaftadine is a H1 histamine receptor antagonist and inhibitor of the release of histamine from mast cells. Decreased chemotaxis and inhibition of eosinophil activation has also been demonstrated.

TargetActionsOrganism
UHistamine H1 receptor
antagonist
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

The protein binding of alcaftadine and the active metabolite are 39.2% and 62.7% respectively.

Metabolism

The metabolism of alcaftadine is mediated by non-CYP450 cytosolic enzymes to the active carboxylic acid metabolite.

Route of elimination

Based on data following oral administration of alcaftadine, the carboxylic acid metabolite is primarily eliminated unchanged in the urine.

Half-life

The elimination half-life of the carboxylic acid metabolite is approximately 2 hours following topical ocular administration.

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
PathwayCategory
Alcaftadine 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
FexinidazoleThe risk or severity of adverse effects can be increased when Alcaftadine is combined with Fexinidazole.
FluoxetineThe risk or severity of QTc prolongation can be increased when Fluoxetine is combined with Alcaftadine.
HaloperidolThe risk or severity of QTc prolongation can be increased when Alcaftadine is combined with Haloperidol.
HydroxyzineThe risk or severity of QTc prolongation can be increased when Alcaftadine is combined with Hydroxyzine.
HyoscyamineAlcaftadine may increase the anticholinergic activities of Hyoscyamine.
LefamulinLefamulin may increase the QTc-prolonging activities of Alcaftadine.
PitolisantAlcaftadine may increase the QTc-prolonging activities of Pitolisant.
PonesimodThe risk or severity of bradycardia can be increased when Ponesimod is combined with Alcaftadine.
TrazodoneThe risk or severity of QTc prolongation can be increased when Trazodone is combined with Alcaftadine.
ZiprasidoneThe risk or severity of QTc prolongation can be increased when Alcaftadine is combined with Ziprasidone.
Interactions
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LastacaftSolution / drops2.5 mg/1mLOphthalmicPhysicians Total Care, Inc.2011-08-19Not applicableUS flag
LastacaftSolution / drops2.5 mg/1mLOphthalmicAllergan, Inc.2010-11-01Not applicableUS flag
LastacaftSolution2.5 mg/1mLOphthalmicVistakon Pharmaceuticals, LLC2010-08-152010-10-13US flag
LastacaftSolution / drops2.5 mg/1mLOphthalmicRebel Distributors2010-11-01Not applicableUS flag

Categories

ATC Codes
S01GX11 — Alcaftadine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzazepines. These are organic compounds containing a benzene ring fused to an azepine ring (unsaturated seven-membered heterocycle with one nitrogen atom replacing a carbon atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzazepines
Sub Class
Not Available
Direct Parent
Benzazepines
Alternative Parents
Carbonylimidazoles / Azepines / Aryl-aldehydes / Piperidines / N-substituted imidazoles / Benzenoids / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
Aldehyde / Amine / Aromatic heteropolycyclic compound / Aryl-aldehyde / Azacycle / Azepine / Azole / Benzazepine / Benzenoid / Heteroaromatic compound
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, tertiary amino compound, aldehyde, imidazobenzazepine (CHEBI:71023)
Affected organisms
Not Available

Chemical Identifiers

UNII
7Z8O94ECSX
CAS number
147084-10-4
InChI Key
MWTBKTRZPHJQLH-UHFFFAOYSA-N
InChI
InChI=1S/C19H21N3O/c1-21-9-6-15(7-10-21)18-17-5-3-2-4-14(17)8-11-22-16(13-23)12-20-19(18)22/h2-5,12-13H,6-11H2,1H3
IUPAC Name
2-(1-methylpiperidin-4-ylidene)-4,7-diazatricyclo[8.4.0.0³,⁷]tetradeca-1(14),3,5,10,12-pentaene-6-carbaldehyde
SMILES
CN1CCC(CC1)=C1C2=NC=C(C=O)N2CCC2=CC=CC=C12

References

General References
  1. Mahvan TD, Buckley WA, Hornecker JR: Alcaftadine for the prevention of itching associated with allergic conjunctivitis. Ann Pharmacother. 2012 Jul-Aug;46(7-8):1025-32. doi: 10.1345/aph.1Q755. Epub 2012 Jul 17. [Article]
  2. Simons FE, Simons KJ: Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011 Dec;128(6):1139-1150.e4. doi: 10.1016/j.jaci.2011.09.005. Epub 2011 Oct 27. [Article]
  3. Hussar DA, Samuel J: Vilazodone hydrochloride, linagliptin, and alcaftadine. J Am Pharm Assoc (2003). 2011 Jul-Aug;51(4):557-9. doi: 10.1331/JAPhA.2011.11534. [Article]
Human Metabolome Database
HMDB0015670
KEGG Drug
D06552
PubChem Compound
19371515
PubChem Substance
99443288
ChemSpider
14201635
RxNav
1000082
ChEBI
71023
ChEMBL
CHEMBL1201747
ZINC
ZINC000011726211
PharmGKB
PA165958399
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alcaftadine
FDA label
Download (146 KB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAllergic Conjunctivitis (AC)3
4Unknown StatusTreatmentAllergic Conjunctivitis (AC)1
4Unknown StatusTreatmentAllergic Conjunctivitis (AC) / Rhinoconjunctivitis1
3CompletedTreatmentAllergic Conjunctivitis (AC)4
3CompletedTreatmentHealthy Volunteers Eligible for Study; Drug Being Developed for Allergic Conjunctivitis1
Not AvailableCompletedNot AvailableAllergic Conjunctivitis (AC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
LiquidOphthalmic2.5 mg/1ml
SolutionOphthalmic2.5 mg/1mL
Solution / dropsOphthalmic2.5 mg/1mL
Solution / dropsOphthalmic
SolutionOphthalmic2.5 mg/mL
SolutionOphthalmic2.5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8664215No2014-03-042027-12-23US flag
US5468743No1995-11-212016-04-20US flag
US10617695No2020-04-142027-03-19US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)556.247 °C at 760 mmHg.# http://www.lookchem.com/Product_842767/CasNo_147084-10-4/Alcaftadine.html#.UXtC3Ct5N_k
water solubilityslightly solubilityFDA Label
logP3.202# http://www.lookchem.com/Product_842767/CasNo_147084-10-4/Alcaftadine.html#.UXtC3Ct5N_k
Predicted Properties
PropertyValueSource
Water Solubility0.333 mg/mLALOGPS
logP2.09ALOGPS
logP2.17ChemAxon
logS-3ALOGPS
pKa (Strongest Basic)7.16ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area38.13 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity102.88 m3·mol-1ChemAxon
Polarizability34.68 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+0.9745
Caco-2 permeable+0.5974
P-glycoprotein substrateSubstrate0.8775
P-glycoprotein inhibitor IInhibitor0.8923
P-glycoprotein inhibitor IIInhibitor0.7024
Renal organic cation transporterInhibitor0.7448
CYP450 2C9 substrateNon-substrate0.7517
CYP450 2D6 substrateNon-substrate0.7096
CYP450 3A4 substrateSubstrate0.613
CYP450 1A2 substrateInhibitor0.6525
CYP450 2C9 inhibitorNon-inhibitor0.6685
CYP450 2D6 inhibitorNon-inhibitor0.6573
CYP450 2C19 inhibitorNon-inhibitor0.7002
CYP450 3A4 inhibitorNon-inhibitor0.8498
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6381
Ames testNon AMES toxic0.561
CarcinogenicityNon-carcinogens0.9681
BiodegradationNot ready biodegradable0.969
Rat acute toxicity2.7266 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6292
hERG inhibition (predictor II)Inhibitor0.5603
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

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Simons FE, Simons KJ: Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011 Dec;128(6):1139-1150.e4. doi: 10.1016/j.jaci.2011.09.005. Epub 2011 Oct 27. [Article]
  2. LASTACAFT [Link]

Drug created on September 14, 2010 16:21 / Updated on February 21, 2021 18:52