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Identification
NameTiotropium
Accession NumberDB01409
TypeSmall Molecule
GroupsApproved
DescriptionTiotropium is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). Tiotropium is a muscarinic receptor antagonist, on topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect.
Structure
Thumb
SynonymsNot Available
External Identifiers
  • BA 679 BR
  • BA-679 BR
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Spirivacapsule18 ug/1oral; respiratory (inhalation)Boehringer Ingelheim Pharmaceuticals Inc.2005-10-11Not applicableUs
Spirivacapsule18 ug/1oral; respiratory (inhalation)Physicians Total Care, Inc.2004-07-14Not applicableUs
Spirivacapsule18 mcginhalationBoehringer Ingelheim (Canada) Ltd Ltee2002-11-21Not applicableCanada
Spirivacapsule18 ug/1oral; respiratory (inhalation)Lake Erie Medical & Surgical Supply DBA Quality Care Products LLC2005-10-11Not applicableUs
Spiriva Respimatspray, metered3.124 ug/1respiratory (inhalation)Boehringer Ingelheim Pharmaceuticals, Inc.2014-09-30Not applicableUs
Spiriva Respimatspray, metered1.562 ug/1respiratory (inhalation)Boehringer Ingelheim Pharmaceuticals, Inc.2015-09-15Not applicableUs
Spiriva Respimatsolution2.5 mcginhalationBoehringer Ingelheim (Canada) Ltd Ltee2014-12-19Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Inspiolto RespimatBoehringer Ingelheim (Canada) Ltd Ltee
Stiolto RespimatBoehringer Ingelheim Pharmaceuticals Inc.
Salts
Name/CASStructureProperties
Tiotropium bromide
136310-93-5
Thumb
  • InChI Key: DQHNAVOVODVIMG-RGECMCKFNA-M
  • Monoisotopic Mass: 471.017362224
  • Average Mass: 472.416
DBSALT000348
Tiotropium bromide monohydrate
ThumbNot applicableDBSALT001524
Categories
UNII0EB439235F
CAS number186691-13-4
WeightAverage: 392.512
Monoisotopic: 392.099024577
Chemical FormulaC19H22NO4S2
InChI KeyLERNTVKEWCAPOY-DZZGSBJMSA-N
InChI
InChI=1S/C19H22NO4S2/c1-20(2)12-9-11(10-13(20)17-16(12)24-17)23-18(21)19(22,14-5-3-7-25-14)15-6-4-8-26-15/h3-8,11-13,16-17,22H,9-10H2,1-2H3/q+1/t11-,12-,13+,16-,17+
IUPAC Name
(1R,2R,4S,5S,7R)-7-{[2-hydroxy-2,2-bis(thiophen-2-yl)acetyl]oxy}-9,9-dimethyl-3-oxa-9-azatricyclo[3.3.1.0²,⁴]nonan-9-ium
SMILES
[H][C@]12O[C@@]1([H])[C@]1([H])C[C@@]([H])(C[C@@]2([H])[N+]1(C)C)OC(=O)C(O)(C1=CC=CS1)C1=CC=CS1
Taxonomy
ClassificationNot classified
Pharmacology
IndicationUsed in the management of chronic obstructive pulmonary disease (COPD).
PharmacodynamicsTiotropium is a long–acting, antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3–receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies prevention of methacholine–induced bronchoconstriction effects were dose–dependent and lasted longer than 24 hours. The bronchodilation following inhalation of tiotropium is predominantly a site–specific effect.
Mechanism of actionTiotropium is a muscarinic receptor antagonist, often referred to as an antimuscarinic or anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors, on topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect.
Related Articles
AbsorptionBioavailability is 19.5% following administration by inhalation. Oral solutions of tiotropium have an absolute bioavailability of 2-3%.
Volume of distribution
  • 32 L/kg
Protein binding72% bound to plasma proteins.
Metabolism

The extent of biotransformation appears to be small. This is evident from a urinary excretion of 74% of unchanged substance after an intravenous dose to young healthy volunteers. Tiotropium, an ester, is nonenzymatically cleaved to the alcohol N–methylscopine and dithienylglycolic acid, neither of which bind to muscarinic receptors. In vitro experiments with human liver microsomes and human hepatocytes suggest that a fraction of the administered dose (74% of an intravenous dose is excreted unchanged in the urine, leaving 25% for metabolism) is metabolized by cytochrome P450–dependent oxidation and subsequent glutathione conjugation to a variety of Phase II metabolites. Via inhibition studies, it is evident that CYP450 2D6 and 3A4 are involved in the metabolic pathway that is responsible for the elimination of a small part of the administered dose.

Route of eliminationIntravenously administered tiotropium was mainly excreted unchanged in urine (74%). After dry powder inhalation, urinary excretion was 14% of the dose, the remainder being mainly non-absorbed drug in the gut which was eliminated via the feces.
Half life5-6 days
Clearance
  • 880 mL/min [young healthy volunteers receiving IV administration]
  • Renal cl=326 mL/min [COPD patients (<58 years)]
  • Renal cl=163 mL/min [COPD patients (>70 years)]
ToxicityNo mortality was observed at inhalation tiotropium doses up to 32.4 mg/kg in mice, 267.7 mg/kg in rats, and 0.6 mg/kg in dogs. These doses correspond to 7,300, 120,000, and 850 times the recommended human daily dose on a mg/m2 basis, respectively.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9173
Blood Brain Barrier+0.5208
Caco-2 permeable+0.5294
P-glycoprotein substrateSubstrate0.7153
P-glycoprotein inhibitor INon-inhibitor0.7514
P-glycoprotein inhibitor IINon-inhibitor0.9762
Renal organic cation transporterNon-inhibitor0.7256
CYP450 2C9 substrateNon-substrate0.6633
CYP450 2D6 substrateNon-substrate0.7533
CYP450 3A4 substrateSubstrate0.6615
CYP450 1A2 substrateNon-inhibitor0.7787
CYP450 2C9 inhibitorNon-inhibitor0.812
CYP450 2D6 inhibitorNon-inhibitor0.8368
CYP450 2C19 inhibitorNon-inhibitor0.7284
CYP450 3A4 inhibitorNon-inhibitor0.7752
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9289
Ames testNon AMES toxic0.6133
CarcinogenicityNon-carcinogens0.9221
BiodegradationNot ready biodegradable0.9319
Rat acute toxicity2.6249 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9957
hERG inhibition (predictor II)Non-inhibitor0.8947
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solutioninhalation
Capsuleinhalation18 mcg
Capsuleoral; respiratory (inhalation)18 ug/1
Solutioninhalation2.5 mcg
Spray, meteredrespiratory (inhalation)1.562 ug/1
Spray, meteredrespiratory (inhalation)3.124 ug/1
Spray, meteredrespiratory (inhalation)
Prices
Unit descriptionCostUnit
Spiriva HandiHaler 30 18 mcg capsule Box223.07USD box
Spiriva HandiHaler 5 18 mcg capsule Box63.64USD box
Spiriva HandiHaler 6 18 mcg capsule Box41.99USD box
Spiriva 18 mcg cp-handihaler6.31USD inhaler
Spiriva 18 mcg Capsule2.2USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2066248 No1998-08-042010-09-08Canada
US5478578 No1992-12-262012-12-26Us
US5964416 No1996-10-042016-10-04Us
US6149054 No1996-12-162016-12-16Us
US6176442 No1996-05-312016-05-31Us
US6453795 No1996-12-052016-12-05Us
US6726124 No1996-10-042016-10-04Us
US6777423 No2001-09-242021-09-24Us
US6846413 No1998-08-282018-08-28Us
US6908928 No2001-09-242021-09-24Us
US6977042 No1998-08-282018-08-28Us
US6988496 No2000-02-232020-02-23Us
US7056916 No2003-12-072023-12-07Us
US7070800 No2002-01-222022-01-22Us
US7104470 No1996-10-042016-10-04Us
US7220742 No2005-05-122025-05-12Us
US7246615 No1996-05-312016-05-31Us
US7284474 No2004-08-262024-08-26Us
US7309707 No2001-09-242021-09-24Us
US7396341 No2006-10-102026-10-10Us
US7491719 No2003-11-102023-11-10Us
US7642268 No2001-09-242021-09-24Us
US7694676 No2007-03-122027-03-12Us
US7727984 No2003-11-102023-11-10Us
US7786111 No2003-11-102023-11-10Us
US7802568 No1999-02-262019-02-26Us
US7837235 No2008-03-132028-03-13Us
US7896264 No2005-05-262025-05-26Us
US7988001 No2001-08-042021-08-04Us
US8022082 No2006-01-192026-01-19Us
US8034809 No2005-05-122025-05-12Us
US8044046 No2003-11-102023-11-10Us
US8733341 No2009-12-162029-12-16Us
US9027967 No2007-03-312027-03-31Us
USRE38912 No2001-10-112021-10-11Us
USRE39820 No1998-01-302018-01-30Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0156 mg/mLALOGPS
logP-0.55ALOGPS
logP-1.8ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)10.35ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area59.06 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity109.18 m3·mol-1ChemAxon
Polarizability39.52 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Rolf Banholzer, “Crystalline tiotropium bromide monohydrate, processes for the preparation thereof, and pharmaceutical compositions.” U.S. Patent US20020169321, issued November 14, 2002.

US20020169321
General ReferencesNot Available
External Links
ATC CodesR03AL06R03BB54R03BB04
AHFS Codes
  • 12:08.08
PDB EntriesNot Available
FDA labelDownload (401 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
1,10-PhenanthrolineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with 1,10-Phenanthroline.
AbirateroneThe metabolism of Tiotropium can be decreased when combined with Abiraterone.
AclidiniumAclidinium may increase the anticholinergic activities of Tiotropium.
AclidiniumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Aclidinium.
AlfentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Alfentanil.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Alphacetylmethadol.
AmbenoniumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Ambenonium.
AmiodaroneThe metabolism of Tiotropium can be decreased when combined with Amiodarone.
Anisotropine MethylbromideAnisotropine Methylbromide may increase the anticholinergic activities of Tiotropium.
Anisotropine MethylbromideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Anisotropine Methylbromide.
AprepitantThe serum concentration of Tiotropium can be increased when it is combined with Aprepitant.
ArtemetherThe metabolism of Tiotropium can be decreased when combined with Artemether.
AtazanavirThe metabolism of Tiotropium can be decreased when combined with Atazanavir.
AtomoxetineThe metabolism of Tiotropium can be decreased when combined with Atomoxetine.
Atracurium besylateAtracurium besylate may increase the anticholinergic activities of Tiotropium.
Atracurium besylateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Atracurium besylate.
AtropineAtropine may increase the anticholinergic activities of Tiotropium.
AtropineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Atropine.
BenactyzineBenactyzine may increase the anticholinergic activities of Tiotropium.
BenactyzineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Benactyzine.
BendroflumethiazideThe serum concentration of Bendroflumethiazide can be increased when it is combined with Tiotropium.
BenzatropineBenzatropine may increase the anticholinergic activities of Tiotropium.
BenzatropineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Benzatropine.
BetaxololThe metabolism of Tiotropium can be decreased when combined with Betaxolol.
BexaroteneThe serum concentration of Tiotropium can be decreased when it is combined with Bexarotene.
BezitramideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Bezitramide.
BiperidenBiperiden may increase the anticholinergic activities of Tiotropium.
BiperidenThe risk or severity of adverse effects can be increased when Tiotropium is combined with Biperiden.
BoceprevirThe metabolism of Tiotropium can be decreased when combined with Boceprevir.
BortezomibThe metabolism of Tiotropium can be decreased when combined with Bortezomib.
BosentanThe serum concentration of Tiotropium can be decreased when it is combined with Bosentan.
Botulinum Toxin Type ATiotropium may increase the anticholinergic activities of Botulinum Toxin Type A.
Botulinum Toxin Type BTiotropium may increase the anticholinergic activities of Botulinum Toxin Type B.
BuprenorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Buprenorphine.
BupropionThe metabolism of Tiotropium can be decreased when combined with Bupropion.
ButorphanolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Butorphanol.
CarbamazepineThe metabolism of Tiotropium can be increased when combined with Carbamazepine.
CarfentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Carfentanil.
CelecoxibThe metabolism of Tiotropium can be decreased when combined with Celecoxib.
CeritinibThe serum concentration of Tiotropium can be increased when it is combined with Ceritinib.
ChloroquineThe metabolism of Tiotropium can be decreased when combined with Chloroquine.
ChlorothiazideThe serum concentration of Chlorothiazide can be increased when it is combined with Tiotropium.
ChlorphenoxamineChlorphenoxamine may increase the anticholinergic activities of Tiotropium.
ChlorphenoxamineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Chlorphenoxamine.
ChlorpromazineThe metabolism of Tiotropium can be decreased when combined with Chlorpromazine.
ChlorthalidoneThe serum concentration of Chlorthalidone can be increased when it is combined with Tiotropium.
CholecalciferolThe metabolism of Tiotropium can be decreased when combined with Cholecalciferol.
CimetidineThe metabolism of Tiotropium can be decreased when combined with Cimetidine.
CimetropiumTiotropium may increase the anticholinergic activities of Cimetropium.
CinacalcetThe metabolism of Tiotropium can be decreased when combined with Cinacalcet.
CitalopramThe metabolism of Tiotropium can be decreased when combined with Citalopram.
ClarithromycinThe metabolism of Tiotropium can be decreased when combined with Clarithromycin.
ClemastineThe metabolism of Tiotropium can be decreased when combined with Clemastine.
ClobazamThe metabolism of Tiotropium can be decreased when combined with Clobazam.
ClomipramineThe metabolism of Tiotropium can be decreased when combined with Clomipramine.
ClotrimazoleThe metabolism of Tiotropium can be decreased when combined with Clotrimazole.
ClozapineThe metabolism of Tiotropium can be decreased when combined with Clozapine.
CobicistatThe serum concentration of Tiotropium can be increased when it is combined with Cobicistat.
CocaineThe metabolism of Tiotropium can be decreased when combined with Cocaine.
CodeineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Codeine.
ConivaptanThe serum concentration of Tiotropium can be increased when it is combined with Conivaptan.
CoumaphosThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Coumaphos.
CrizotinibThe metabolism of Tiotropium can be decreased when combined with Crizotinib.
CyclopentolateCyclopentolate may increase the anticholinergic activities of Tiotropium.
CyclopentolateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Cyclopentolate.
CyclosporineThe metabolism of Tiotropium can be decreased when combined with Cyclosporine.
DabrafenibThe serum concentration of Tiotropium can be decreased when it is combined with Dabrafenib.
DarifenacinDarifenacin may increase the anticholinergic activities of Tiotropium.
DarifenacinThe risk or severity of adverse effects can be increased when Tiotropium is combined with Darifenacin.
DarunavirThe serum concentration of Tiotropium can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Tiotropium can be increased when it is combined with Dasatinib.
DecamethoniumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Decamethonium.
DeferasiroxThe serum concentration of Tiotropium can be decreased when it is combined with Deferasirox.
DelavirdineThe metabolism of Tiotropium can be decreased when combined with Delavirdine.
DemecariumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Demecarium.
DesipramineThe metabolism of Tiotropium can be decreased when combined with Desipramine.
DesloratadineDesloratadine may increase the anticholinergic activities of Tiotropium.
DesloratadineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Desloratadine.
DexamethasoneThe serum concentration of Tiotropium can be decreased when it is combined with Dexamethasone.
DexetimideDexetimide may increase the anticholinergic activities of Tiotropium.
DexetimideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dexetimide.
DextromoramideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dextromoramide.
DextropropoxypheneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dextropropoxyphene.
DezocineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dezocine.
DichlorvosThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Dichlorvos.
DicyclomineDicyclomine may increase the anticholinergic activities of Tiotropium.
DicyclomineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dicyclomine.
DihydrocodeineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dihydrocodeine.
DihydroergotamineThe metabolism of Tiotropium can be decreased when combined with Dihydroergotamine.
DihydroetorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dihydroetorphine.
DihydromorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dihydromorphine.
DiltiazemThe metabolism of Tiotropium can be decreased when combined with Diltiazem.
DiphenhydramineThe metabolism of Tiotropium can be decreased when combined with Diphenhydramine.
DiphenoxylateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Diphenoxylate.
DonepezilThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Donepezil.
DoxycyclineThe metabolism of Tiotropium can be decreased when combined with Doxycycline.
DPDPEThe risk or severity of adverse effects can be increased when Tiotropium is combined with DPDPE.
DronabinolTiotropium may increase the tachycardic activities of Dronabinol.
DronedaroneThe metabolism of Tiotropium can be decreased when combined with Dronedarone.
DuloxetineThe metabolism of Tiotropium can be decreased when combined with Duloxetine.
EchothiophateThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Echothiophate.
EdrophoniumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Edrophonium.
EfavirenzThe serum concentration of Tiotropium can be decreased when it is combined with Efavirenz.
EliglustatThe metabolism of Tiotropium can be decreased when combined with Eliglustat.
EluxadolineTiotropium may increase the constipating activities of Eluxadoline.
EnzalutamideThe serum concentration of Tiotropium can be decreased when it is combined with Enzalutamide.
ErythromycinThe metabolism of Tiotropium can be decreased when combined with Erythromycin.
Eslicarbazepine acetateThe serum concentration of Tiotropium can be decreased when it is combined with Eslicarbazepine acetate.
EthopropazineEthopropazine may increase the anticholinergic activities of Tiotropium.
EthopropazineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Ethopropazine.
EthylmorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Ethylmorphine.
EtorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Etorphine.
EtravirineThe serum concentration of Tiotropium can be decreased when it is combined with Etravirine.
FentanylThe risk or severity of adverse effects can be increased when Tiotropium is combined with Fentanyl.
FenthionThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Fenthion.
FesoterodineFesoterodine may increase the anticholinergic activities of Tiotropium.
FesoterodineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Fesoterodine.
FluconazoleThe metabolism of Tiotropium can be decreased when combined with Fluconazole.
FluoxetineThe metabolism of Tiotropium can be decreased when combined with Fluoxetine.
FluvoxamineThe metabolism of Tiotropium can be decreased when combined with Fluvoxamine.
FosamprenavirThe metabolism of Tiotropium can be decreased when combined with Fosamprenavir.
FosaprepitantThe serum concentration of Tiotropium can be increased when it is combined with Fosaprepitant.
FosphenytoinThe metabolism of Tiotropium can be increased when combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Tiotropium can be increased when it is combined with Fusidic Acid.
GalantamineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Galantamine.
Gallamine TriethiodideGallamine Triethiodide may increase the anticholinergic activities of Tiotropium.
Gallamine TriethiodideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Gallamine Triethiodide.
Ginkgo bilobaThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Ginkgo biloba.
Glucagon recombinantThe risk or severity of adverse effects can be increased when Tiotropium is combined with Glucagon recombinant.
GlycopyrroniumGlycopyrronium may increase the anticholinergic activities of Tiotropium.
HaloperidolThe metabolism of Tiotropium can be decreased when combined with Haloperidol.
HeroinThe risk or severity of adverse effects can be increased when Tiotropium is combined with Heroin.
HexamethoniumHexamethonium may increase the anticholinergic activities of Tiotropium.
HexamethoniumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Hexamethonium.
HomatropineHomatropine may increase the anticholinergic activities of Tiotropium.
HomatropineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Homatropine.
Huperzine AThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Huperzine A.
HydrochlorothiazideThe serum concentration of Hydrochlorothiazide can be increased when it is combined with Tiotropium.
HydrocodoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Hydrocodone.
HydroflumethiazideThe serum concentration of Hydroflumethiazide can be increased when it is combined with Tiotropium.
HydromorphoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Hydromorphone.
HyoscyamineHyoscyamine may increase the anticholinergic activities of Tiotropium.
HyoscyamineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Hyoscyamine.
IdelalisibThe serum concentration of Tiotropium can be increased when it is combined with Idelalisib.
ImatinibThe metabolism of Tiotropium can be decreased when combined with Imatinib.
ImipramineThe metabolism of Tiotropium can be decreased when combined with Imipramine.
IndapamideThe serum concentration of Indapamide can be increased when it is combined with Tiotropium.
IndinavirThe metabolism of Tiotropium can be decreased when combined with Indinavir.
Ipratropium bromideIpratropium bromide may increase the anticholinergic activities of Tiotropium.
Ipratropium bromideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Ipratropium bromide.
IsavuconazoniumThe metabolism of Tiotropium can be decreased when combined with Isavuconazonium.
IsoflurophateThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Isoflurophate.
IsoniazidThe metabolism of Tiotropium can be decreased when combined with Isoniazid.
IsradipineThe metabolism of Tiotropium can be decreased when combined with Isradipine.
ItoprideThe therapeutic efficacy of Itopride can be decreased when used in combination with Tiotropium.
ItraconazoleThe metabolism of Tiotropium can be decreased when combined with Itraconazole.
IvacaftorThe serum concentration of Tiotropium can be increased when it is combined with Ivacaftor.
KetobemidoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Ketobemidone.
KetoconazoleThe metabolism of Tiotropium can be decreased when combined with Ketoconazole.
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Levomethadyl Acetate.
LevorphanolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Levorphanol.
LofentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Lofentanil.
LopinavirThe metabolism of Tiotropium can be decreased when combined with Lopinavir.
LorcaserinThe metabolism of Tiotropium can be decreased when combined with Lorcaserin.
LovastatinThe metabolism of Tiotropium can be decreased when combined with Lovastatin.
LuliconazoleThe serum concentration of Tiotropium can be increased when it is combined with Luliconazole.
LumefantrineThe metabolism of Tiotropium can be decreased when combined with Lumefantrine.
MalathionThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Malathion.
MecamylamineMecamylamine may increase the anticholinergic activities of Tiotropium.
MecamylamineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Mecamylamine.
MefloquineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Mefloquine.
MemantineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Memantine.
MethadoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Methadone.
MethadoneThe metabolism of Tiotropium can be decreased when combined with Methadone.
Methadyl AcetateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Methadyl Acetate.
MethanthelineMethantheline may increase the anticholinergic activities of Tiotropium.
MethanthelineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Methantheline.
MethotrimeprazineThe metabolism of Tiotropium can be decreased when combined with Methotrimeprazine.
MethyclothiazideThe serum concentration of Methyclothiazide can be increased when it is combined with Tiotropium.
MetixeneMetixene may increase the anticholinergic activities of Tiotropium.
MetixeneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Metixene.
MetolazoneThe serum concentration of Metolazone can be increased when it is combined with Tiotropium.
MetoprololThe metabolism of Tiotropium can be decreased when combined with Metoprolol.
MianserinMianserin may increase the anticholinergic activities of Tiotropium.
MifepristoneThe metabolism of Tiotropium can be decreased when combined with Mifepristone.
MinaprineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Minaprine.
MirabegronThe risk or severity of adverse effects can be increased when Tiotropium is combined with Mirabegron.
MirabegronThe metabolism of Tiotropium can be decreased when combined with Mirabegron.
MitotaneThe serum concentration of Tiotropium can be decreased when it is combined with Mitotane.
ModafinilThe serum concentration of Tiotropium can be decreased when it is combined with Modafinil.
MorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Morphine.
N-butylscopolammonium bromideN-butylscopolammonium bromide may increase the anticholinergic activities of Tiotropium.
N-butylscopolammonium bromideThe risk or severity of adverse effects can be increased when Tiotropium is combined with N-butylscopolammonium bromide.
NabiloneTiotropium may increase the tachycardic activities of Nabilone.
NafcillinThe serum concentration of Tiotropium can be decreased when it is combined with Nafcillin.
NalbuphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Nalbuphine.
NefazodoneThe metabolism of Tiotropium can be decreased when combined with Nefazodone.
NelfinavirThe metabolism of Tiotropium can be decreased when combined with Nelfinavir.
NeostigmineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Neostigmine.
NetupitantThe serum concentration of Tiotropium can be increased when it is combined with Netupitant.
NevirapineThe metabolism of Tiotropium can be decreased when combined with Nevirapine.
NicardipineThe metabolism of Tiotropium can be decreased when combined with Nicardipine.
NilotinibThe metabolism of Tiotropium can be decreased when combined with Nilotinib.
NormethadoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Normethadone.
NVA237NVA237 may increase the anticholinergic activities of Tiotropium.
NVA237The risk or severity of adverse effects can be increased when Tiotropium is combined with NVA237.
OlaparibThe metabolism of Tiotropium can be decreased when combined with Olaparib.
OpiumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Opium.
OrphenadrineOrphenadrine may increase the anticholinergic activities of Tiotropium.
OrphenadrineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Orphenadrine.
OsimertinibThe serum concentration of Tiotropium can be increased when it is combined with Osimertinib.
OxybutyninOxybutynin may increase the anticholinergic activities of Tiotropium.
OxybutyninThe risk or severity of adverse effects can be increased when Tiotropium is combined with Oxybutynin.
OxycodoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Oxycodone.
OxymorphoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Oxymorphone.
OxyphenoniumOxyphenonium may increase the anticholinergic activities of Tiotropium.
OxyphenoniumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Oxyphenonium.
PalbociclibThe serum concentration of Tiotropium can be increased when it is combined with Palbociclib.
PancuroniumPancuronium may increase the anticholinergic activities of Tiotropium.
PancuroniumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Pancuronium.
PanobinostatThe metabolism of Tiotropium can be decreased when combined with Panobinostat.
ParoxetineThe metabolism of Tiotropium can be decreased when combined with Paroxetine.
Peginterferon alfa-2bThe serum concentration of Tiotropium can be decreased when it is combined with Peginterferon alfa-2b.
PentazocineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Pentazocine.
PentobarbitalThe metabolism of Tiotropium can be increased when combined with Pentobarbital.
PentoliniumPentolinium may increase the anticholinergic activities of Tiotropium.
PentoliniumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Pentolinium.
PethidineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Pethidine.
PhenobarbitalThe metabolism of Tiotropium can be increased when combined with Phenobarbital.
PhenytoinThe metabolism of Tiotropium can be increased when combined with Phenytoin.
PhysostigmineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Physostigmine.
PipecuroniumPipecuronium may increase the anticholinergic activities of Tiotropium.
PipecuroniumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Pipecuronium.
PirenzepinePirenzepine may increase the anticholinergic activities of Tiotropium.
PirenzepineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Pirenzepine.
PolythiazideThe serum concentration of Polythiazide can be increased when it is combined with Tiotropium.
PosaconazoleThe metabolism of Tiotropium can be decreased when combined with Posaconazole.
Potassium ChlorideTiotropium may increase the ulcerogenic activities of Potassium Chloride.
PramlintidePramlintide may increase the anticholinergic activities of Tiotropium.
PrimidoneThe metabolism of Tiotropium can be increased when combined with Primidone.
ProcyclidineProcyclidine may increase the anticholinergic activities of Tiotropium.
ProcyclidineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Procyclidine.
PromazineThe metabolism of Tiotropium can be decreased when combined with Promazine.
PropanthelinePropantheline may increase the anticholinergic activities of Tiotropium.
PropanthelineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Propantheline.
PyridostigmineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Pyridostigmine.
QuinethazoneThe serum concentration of Quinethazone can be increased when it is combined with Tiotropium.
QuinidineQuinidine may increase the anticholinergic activities of Tiotropium.
QuinidineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Quinidine.
QuinineThe metabolism of Tiotropium can be decreased when combined with Quinine.
RamosetronTiotropium may increase the constipating activities of Ramosetron.
RanolazineThe metabolism of Tiotropium can be decreased when combined with Ranolazine.
RemifentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Remifentanil.
RifabutinThe metabolism of Tiotropium can be increased when combined with Rifabutin.
RifampicinThe metabolism of Tiotropium can be increased when combined with Rifampicin.
RifapentineThe metabolism of Tiotropium can be increased when combined with Rifapentine.
RitonavirThe metabolism of Tiotropium can be decreased when combined with Ritonavir.
RivastigmineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Rivastigmine.
RolapitantThe metabolism of Tiotropium can be decreased when combined with Rolapitant.
RopiniroleThe metabolism of Tiotropium can be decreased when combined with Ropinirole.
SaquinavirThe metabolism of Tiotropium can be decreased when combined with Saquinavir.
ScopolamineScopolamine may increase the anticholinergic activities of Tiotropium.
ScopolamineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Scopolamine.
Scopolamine butylbromideScopolamine butylbromide may increase the anticholinergic activities of Tiotropium.
Scopolamine butylbromideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Scopolamine butylbromide.
SecretinThe therapeutic efficacy of Secretin can be decreased when used in combination with Tiotropium.
SertralineThe metabolism of Tiotropium can be decreased when combined with Sertraline.
SildenafilThe metabolism of Tiotropium can be decreased when combined with Sildenafil.
SiltuximabThe serum concentration of Tiotropium can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Tiotropium can be increased when it is combined with Simeprevir.
SolifenacinSolifenacin may increase the anticholinergic activities of Tiotropium.
SolifenacinThe risk or severity of adverse effects can be increased when Tiotropium is combined with Solifenacin.
St. John's WortThe serum concentration of Tiotropium can be decreased when it is combined with St. John&#39;s Wort.
StiripentolThe serum concentration of Tiotropium can be increased when it is combined with Stiripentol.
SufentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Sufentanil.
SulfisoxazoleThe metabolism of Tiotropium can be decreased when combined with Sulfisoxazole.
SulpirideThe therapeutic efficacy of Sulpiride can be decreased when used in combination with Tiotropium.
TacrineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Tacrine.
TapentadolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Tapentadol.
TelaprevirThe metabolism of Tiotropium can be decreased when combined with Telaprevir.
TelithromycinThe metabolism of Tiotropium can be decreased when combined with Telithromycin.
TerbinafineThe metabolism of Tiotropium can be decreased when combined with Terbinafine.
ThioridazineThe metabolism of Tiotropium can be decreased when combined with Thioridazine.
TiclopidineThe metabolism of Tiotropium can be decreased when combined with Ticlopidine.
TipranavirThe metabolism of Tiotropium can be decreased when combined with Tipranavir.
TocilizumabThe serum concentration of Tiotropium can be decreased when it is combined with Tocilizumab.
TolterodineTolterodine may increase the anticholinergic activities of Tiotropium.
TolterodineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Tolterodine.
TopiramateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Topiramate.
TramadolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Tramadol.
TranylcypromineThe metabolism of Tiotropium can be decreased when combined with Tranylcypromine.
TrichlorfonThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Trichlorfon.
TrichlormethiazideThe serum concentration of Trichlormethiazide can be increased when it is combined with Tiotropium.
TrihexyphenidylTrihexyphenidyl may increase the anticholinergic activities of Tiotropium.
TrihexyphenidylThe risk or severity of adverse effects can be increased when Tiotropium is combined with Trihexyphenidyl.
TrimethaphanTrimethaphan may increase the anticholinergic activities of Tiotropium.
TrimethaphanThe risk or severity of adverse effects can be increased when Tiotropium is combined with Trimethaphan.
TropicamideTropicamide may increase the anticholinergic activities of Tiotropium.
TropicamideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Tropicamide.
TrospiumTrospium may increase the anticholinergic activities of Tiotropium.
TrospiumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Trospium.
TubocurarineTubocurarine may increase the anticholinergic activities of Tiotropium.
TubocurarineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Tubocurarine.
UmeclidiniumUmeclidinium may increase the anticholinergic activities of Tiotropium.
UmeclidiniumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Umeclidinium.
VecuroniumVecuronium may increase the anticholinergic activities of Tiotropium.
VecuroniumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Vecuronium.
VenlafaxineThe metabolism of Tiotropium can be decreased when combined with Venlafaxine.
VerapamilThe metabolism of Tiotropium can be decreased when combined with Verapamil.
VoriconazoleThe metabolism of Tiotropium can be decreased when combined with Voriconazole.
ZiprasidoneThe metabolism of Tiotropium can be decreased when combined with Ziprasidone.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Hansel TT, Barnes PJ: Tiotropium bromide: a novel once-daily anticholinergic bronchodilator for the treatment of COPD. Drugs Today (Barc). 2002 Sep;38(9):585-600. [PubMed:12582447 ]
  3. Barnes PJ: Tiotropium bromide. Expert Opin Investig Drugs. 2001 Apr;10(4):733-40. [PubMed:11281822 ]
  4. Barnes PJ, Belvisi MG, Mak JC, Haddad EB, O'Connor B: Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sci. 1995;56(11-12):853-9. [PubMed:10188785 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
References
  1. Hansel TT, Barnes PJ: Tiotropium bromide: a novel once-daily anticholinergic bronchodilator for the treatment of COPD. Drugs Today (Barc). 2002 Sep;38(9):585-600. [PubMed:12582447 ]
  2. Barnes PJ: Tiotropium bromide. Expert Opin Investig Drugs. 2001 Apr;10(4):733-40. [PubMed:11281822 ]
  3. Barnes PJ, Belvisi MG, Mak JC, Haddad EB, O'Connor B: Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sci. 1995;56(11-12):853-9. [PubMed:10188785 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then trigge...
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
References
  1. Hansel TT, Barnes PJ: Tiotropium bromide: a novel once-daily anticholinergic bronchodilator for the treatment of COPD. Drugs Today (Barc). 2002 Sep;38(9):585-600. [PubMed:12582447 ]
  2. Barnes PJ, Belvisi MG, Mak JC, Haddad EB, O'Connor B: Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sci. 1995;56(11-12):853-9. [PubMed:10188785 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Symporter activity
Specific Function:
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3.
Gene Name:
SLC22A5
Uniprot ID:
O76082
Molecular Weight:
62751.08 Da
References
  1. Nakamura T, Nakanishi T, Haruta T, Shirasaka Y, Keogh JP, Tamai I: Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm. 2010 Feb 1;7(1):187-95. doi: 10.1021/mp900206j. [PubMed:20020740 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Symporter activity
Specific Function:
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET).
Gene Name:
SLC22A4
Uniprot ID:
Q9H015
Molecular Weight:
62154.48 Da
References
  1. Nakamura T, Nakanishi T, Haruta T, Shirasaka Y, Keogh JP, Tamai I: Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm. 2010 Feb 1;7(1):187-95. doi: 10.1021/mp900206j. [PubMed:20020740 ]
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Drug created on July 17, 2007 06:36 / Updated on September 29, 2016 02:28