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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)Lake Erie Medical & Surgical Supply DBA Quality Care Products LLC2005-10-11Not applicableUs
SpirivaCapsule18 ug/1Oral; Respiratory (inhalation)Physicians Total Care, Inc.2004-07-14Not applicableUs
SpirivaCapsule18 mcgRespiratory (inhalation)Boehringer Ingelheim (Canada) Ltd Ltee2002-11-21Not applicableCanada
Spiriva RespimatSolution2.5 mcgRespiratory (inhalation)Boehringer Ingelheim (Canada) Ltd Ltee2014-12-19Not applicableCanada
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
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
Pharmacology
IndicationUsed in the management of chronic obstructive pulmonary disease (COPD).
Structured Indications
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Muscarinic acetylcholine receptor M3Proteinyes
antagonist
HumanP20309 details
Muscarinic acetylcholine receptor M1Proteinunknown
antagonist
HumanP11229 details
Muscarinic acetylcholine receptor M2Proteinunknown
antagonist
HumanP08172 details
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
Interactions
Drug Interactions
DrugInteractionDrug group
1,10-PhenanthrolineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with 1,10-Phenanthroline.Experimental
AbirateroneThe serum concentration of Tiotropium can be increased when it is combined with Abiraterone.Approved
AclidiniumAclidinium may increase the anticholinergic activities of Tiotropium.Approved
AlfentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Alfentanil.Approved, Illicit
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Alphacetylmethadol.Experimental, Illicit
AmbenoniumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Ambenonium.Approved
AmiodaroneThe metabolism of Tiotropium can be decreased when combined with Amiodarone.Approved, Investigational
Anisotropine MethylbromideAnisotropine Methylbromide may increase the anticholinergic activities of Tiotropium.Approved
AprepitantThe serum concentration of Tiotropium can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe metabolism of Tiotropium can be decreased when combined with Artemether.Approved
AtazanavirThe metabolism of Tiotropium can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Tiotropium can be decreased when combined with Atomoxetine.Approved
Atracurium besylateAtracurium besylate may increase the anticholinergic activities of Tiotropium.Approved
AtropineAtropine may increase the anticholinergic activities of Tiotropium.Approved, Vet Approved
BenactyzineBenactyzine may increase the anticholinergic activities of Tiotropium.Withdrawn
BendroflumethiazideThe serum concentration of Bendroflumethiazide can be increased when it is combined with Tiotropium.Approved
BenzatropineBenzatropine may increase the anticholinergic activities of Tiotropium.Approved
BetaxololThe metabolism of Tiotropium can be decreased when combined with Betaxolol.Approved
BexaroteneThe serum concentration of Tiotropium can be decreased when it is combined with Bexarotene.Approved, Investigational
BezitramideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Bezitramide.Experimental, Illicit, Withdrawn
BiperidenBiperiden may increase the anticholinergic activities of Tiotropium.Approved
BoceprevirThe metabolism of Tiotropium can be decreased when combined with Boceprevir.Approved
BortezomibThe metabolism of Tiotropium can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Tiotropium can be decreased when it is combined with Bosentan.Approved, Investigational
Botulinum Toxin Type ATiotropium may increase the anticholinergic activities of Botulinum Toxin Type A.Approved, Investigational
Botulinum Toxin Type BTiotropium may increase the anticholinergic activities of Botulinum Toxin Type B.Approved
BuprenorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BupropionThe metabolism of Tiotropium can be decreased when combined with Bupropion.Approved
ButorphanolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Butorphanol.Approved, Illicit, Vet Approved
CarbamazepineThe metabolism of Tiotropium can be increased when combined with Carbamazepine.Approved, Investigational
CarfentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Carfentanil.Illicit, Vet Approved
CelecoxibThe metabolism of Tiotropium can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Tiotropium can be increased when it is combined with Ceritinib.Approved
ChloroquineThe metabolism of Tiotropium can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorothiazideThe serum concentration of Chlorothiazide can be increased when it is combined with Tiotropium.Approved, Vet Approved
ChlorphenoxamineChlorphenoxamine may increase the anticholinergic activities of Tiotropium.Withdrawn
ChlorpromazineThe metabolism of Tiotropium can be decreased when combined with Chlorpromazine.Approved, Vet Approved
ChlorthalidoneThe serum concentration of Chlorthalidone can be increased when it is combined with Tiotropium.Approved
CholecalciferolThe metabolism of Tiotropium can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Tiotropium can be decreased when combined with Cimetidine.Approved
CimetropiumTiotropium may increase the anticholinergic activities of Cimetropium.Experimental
CinacalcetThe metabolism of Tiotropium can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Tiotropium can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Tiotropium can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Tiotropium can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Tiotropium can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Tiotropium can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Tiotropium can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Tiotropium can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Tiotropium can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Tiotropium can be decreased when combined with Cocaine.Approved, Illicit
CodeineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Codeine.Approved, Illicit
ConivaptanThe serum concentration of Tiotropium can be increased when it is combined with Conivaptan.Approved, Investigational
CoumaphosThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Coumaphos.Vet Approved
CrizotinibThe metabolism of Tiotropium can be decreased when combined with Crizotinib.Approved
CyclopentolateCyclopentolate may increase the anticholinergic activities of Tiotropium.Approved
CyclosporineThe metabolism of Tiotropium can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Tiotropium can be decreased when it is combined with Dabrafenib.Approved
DarifenacinDarifenacin may increase the anticholinergic activities of Tiotropium.Approved, Investigational
DarunavirThe serum concentration of Tiotropium can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Tiotropium can be increased when it is combined with Dasatinib.Approved, Investigational
DecamethoniumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Decamethonium.Approved
DeferasiroxThe serum concentration of Tiotropium can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Tiotropium can be decreased when combined with Delavirdine.Approved
DemecariumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Demecarium.Approved
DesipramineThe metabolism of Tiotropium can be decreased when combined with Desipramine.Approved
DesloratadineDesloratadine may increase the anticholinergic activities of Tiotropium.Approved, Investigational
DexamethasoneThe serum concentration of Tiotropium can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DexetimideDexetimide may increase the anticholinergic activities of Tiotropium.Withdrawn
DextromoramideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dextromoramide.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dextropropoxyphene.Approved, Illicit, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dezocine.Approved
DichlorvosThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Dichlorvos.Vet Approved
DicyclomineDicyclomine may increase the anticholinergic activities of Tiotropium.Approved
DihydrocodeineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dihydrocodeine.Approved, Illicit
DihydroergotamineThe metabolism of Tiotropium can be decreased when combined with Dihydroergotamine.Approved
DihydroetorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dihydroetorphine.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Dihydromorphine.Experimental, Illicit
DiltiazemThe metabolism of Tiotropium can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Tiotropium can be decreased when combined with Diphenhydramine.Approved
DiphenoxylateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Diphenoxylate.Approved, Illicit
DonepezilThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Donepezil.Approved
DoxycyclineThe metabolism of Tiotropium can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DPDPEThe risk or severity of adverse effects can be increased when Tiotropium is combined with DPDPE.Investigational
DronabinolTiotropium may increase the tachycardic activities of Dronabinol.Approved, Illicit
DronedaroneThe metabolism of Tiotropium can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Tiotropium can be decreased when combined with Duloxetine.Approved
EchothiophateThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Echothiophate.Approved
EdrophoniumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Edrophonium.Approved
EfavirenzThe serum concentration of Tiotropium can be decreased when it is combined with Efavirenz.Approved, Investigational
EliglustatThe metabolism of Tiotropium can be decreased when combined with Eliglustat.Approved
EluxadolineTiotropium may increase the constipating activities of Eluxadoline.Approved
EnzalutamideThe serum concentration of Tiotropium can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Tiotropium can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Tiotropium can be decreased when it is combined with Eslicarbazepine acetate.Approved
EthopropazineEthopropazine may increase the anticholinergic activities of Tiotropium.Approved
EthylmorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Ethylmorphine.Approved, Illicit
EtorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Etorphine.Illicit, Vet Approved
EtravirineThe serum concentration of Tiotropium can be decreased when it is combined with Etravirine.Approved
FentanylThe risk or severity of adverse effects can be increased when Tiotropium is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FenthionThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Fenthion.Vet Approved
FesoterodineFesoterodine may increase the anticholinergic activities of Tiotropium.Approved
FluconazoleThe metabolism of Tiotropium can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Tiotropium can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Tiotropium can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Tiotropium can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Tiotropium can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Tiotropium can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Tiotropium can be increased when it is combined with Fusidic Acid.Approved
GalantamineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Galantamine.Approved
Gallamine TriethiodideGallamine Triethiodide may increase the anticholinergic activities of Tiotropium.Approved
Ginkgo bilobaThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Ginkgo biloba.Approved, Nutraceutical
Glucagon recombinantThe risk or severity of adverse effects can be increased when Tiotropium is combined with Glucagon recombinant.Approved
GlycopyrroniumGlycopyrronium may increase the anticholinergic activities of Tiotropium.Approved, Investigational, Vet Approved
HaloperidolThe metabolism of Tiotropium can be decreased when combined with Haloperidol.Approved
HeroinThe risk or severity of adverse effects can be increased when Tiotropium is combined with Heroin.Approved, Illicit
HexamethoniumHexamethonium may increase the anticholinergic activities of Tiotropium.Experimental
HomatropineHomatropine may increase the anticholinergic activities of Tiotropium.Approved
Huperzine AThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Huperzine A.Investigational
HydrochlorothiazideThe serum concentration of Hydrochlorothiazide can be increased when it is combined with Tiotropium.Approved, Vet Approved
HydrocodoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Hydrocodone.Approved, Illicit
HydroflumethiazideThe serum concentration of Hydroflumethiazide can be increased when it is combined with Tiotropium.Approved
HydromorphoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Hydromorphone.Approved, Illicit
HyoscyamineHyoscyamine may increase the anticholinergic activities of Tiotropium.Approved
IdelalisibThe serum concentration of Tiotropium can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Tiotropium can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Tiotropium can be decreased when combined with Imipramine.Approved
IndapamideThe serum concentration of Indapamide can be increased when it is combined with Tiotropium.Approved
IndinavirThe metabolism of Tiotropium can be decreased when combined with Indinavir.Approved
Ipratropium bromideIpratropium bromide may increase the anticholinergic activities of Tiotropium.Approved
IsavuconazoniumThe metabolism of Tiotropium can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoflurophateThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Isoflurophate.Approved, Withdrawn
IsoniazidThe metabolism of Tiotropium can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Tiotropium can be decreased when combined with Isradipine.Approved
ItoprideThe therapeutic efficacy of Itopride can be decreased when used in combination with Tiotropium.Investigational
ItraconazoleThe metabolism of Tiotropium can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Tiotropium can be increased when it is combined with Ivacaftor.Approved
KetobemidoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Ketobemidone.Approved
KetoconazoleThe metabolism of Tiotropium can be decreased when combined with Ketoconazole.Approved, Investigational
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Levomethadyl Acetate.Approved
LevorphanolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Levorphanol.Approved
LofentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Lofentanil.Illicit
LopinavirThe metabolism of Tiotropium can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Tiotropium can be decreased when combined with Lorcaserin.Approved
LovastatinThe metabolism of Tiotropium can be decreased when combined with Lovastatin.Approved, Investigational
LoxapineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Loxapine.Approved
LuliconazoleThe serum concentration of Tiotropium can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Tiotropium can be increased when combined with Lumacaftor.Approved
LumefantrineThe metabolism of Tiotropium can be decreased when combined with Lumefantrine.Approved
MalathionThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Malathion.Approved, Investigational
MecamylamineMecamylamine may increase the anticholinergic activities of Tiotropium.Approved
MefloquineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Mefloquine.Approved
MemantineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Memantine.Approved, Investigational
MethadoneThe metabolism of Tiotropium can be decreased when combined with Methadone.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Methadyl Acetate.Approved, Illicit
Methanesulfonyl FluorideThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Methanesulfonyl Fluoride.Investigational
MethanthelineMethantheline may increase the anticholinergic activities of Tiotropium.Approved
MethotrimeprazineThe metabolism of Tiotropium can be decreased when combined with Methotrimeprazine.Approved
MethyclothiazideThe serum concentration of Methyclothiazide can be increased when it is combined with Tiotropium.Approved
MetixeneMetixene may increase the anticholinergic activities of Tiotropium.Approved
MetolazoneThe serum concentration of Metolazone can be increased when it is combined with Tiotropium.Approved
MetoprololThe metabolism of Tiotropium can be decreased when combined with Metoprolol.Approved, Investigational
MianserinMianserin may increase the anticholinergic activities of Tiotropium.Approved
MifepristoneThe serum concentration of Tiotropium can be increased when it is combined with Mifepristone.Approved, Investigational
MinaprineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Minaprine.Approved
MirabegronThe risk or severity of adverse effects can be increased when Tiotropium is combined with Mirabegron.Approved
MitotaneThe serum concentration of Tiotropium can be decreased when it is combined with Mitotane.Approved
ModafinilThe serum concentration of Tiotropium can be decreased when it is combined with Modafinil.Approved, Investigational
MorphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Morphine.Approved, Investigational
N-butylscopolammonium bromideN-butylscopolammonium bromide may increase the anticholinergic activities of Tiotropium.Vet Approved
NabiloneTiotropium may increase the tachycardic activities of Nabilone.Approved, Investigational
NafcillinThe serum concentration of Tiotropium can be decreased when it is combined with Nafcillin.Approved
NalbuphineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Nalbuphine.Approved
NefazodoneThe metabolism of Tiotropium can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Tiotropium can be decreased when combined with Nelfinavir.Approved
NeostigmineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Neostigmine.Approved, Vet Approved
NetupitantThe serum concentration of Tiotropium can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Tiotropium can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Tiotropium can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Tiotropium can be decreased when combined with Nilotinib.Approved, Investigational
NormethadoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Normethadone.Approved, Illicit
NVA237NVA237 may increase the anticholinergic activities of Tiotropium.Investigational
OlaparibThe metabolism of Tiotropium can be decreased when combined with Olaparib.Approved
OpiumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Opium.Approved, Illicit
OrphenadrineOrphenadrine may increase the anticholinergic activities of Tiotropium.Approved
OsimertinibThe serum concentration of Tiotropium can be increased when it is combined with Osimertinib.Approved
OxybutyninOxybutynin may increase the anticholinergic activities of Tiotropium.Approved, Investigational
OxycodoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Oxycodone.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Tiotropium is combined with Oxymorphone.Approved, Investigational, Vet Approved
OxyphenoniumOxyphenonium may increase the anticholinergic activities of Tiotropium.Approved
PalbociclibThe serum concentration of Tiotropium can be increased when it is combined with Palbociclib.Approved
PancuroniumPancuronium may increase the anticholinergic activities of Tiotropium.Approved
PanobinostatThe serum concentration of Tiotropium can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Tiotropium can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Tiotropium can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentazocineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Pentazocine.Approved, Vet Approved
PentobarbitalThe metabolism of Tiotropium can be increased when combined with Pentobarbital.Approved, Vet Approved
PentoliniumPentolinium may increase the anticholinergic activities of Tiotropium.Approved
PethidineThe risk or severity of adverse effects can be increased when Tiotropium is combined with Pethidine.Approved
PhenobarbitalThe metabolism of Tiotropium can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Tiotropium can be increased when combined with Phenytoin.Approved, Vet Approved
PhysostigmineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Physostigmine.Approved
PipecuroniumPipecuronium may increase the anticholinergic activities of Tiotropium.Approved
PirenzepinePirenzepine may increase the anticholinergic activities of Tiotropium.Approved
PiritramideThe risk or severity of adverse effects can be increased when Tiotropium is combined with Piritramide.Investigational
PolythiazideThe serum concentration of Polythiazide can be increased when it is combined with Tiotropium.Approved
PosaconazoleThe metabolism of Tiotropium can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
Potassium ChlorideTiotropium may increase the ulcerogenic activities of Potassium Chloride.Approved, Withdrawn
PramlintidePramlintide may increase the anticholinergic activities of Tiotropium.Approved, Investigational
PrimidoneThe metabolism of Tiotropium can be increased when combined with Primidone.Approved, Vet Approved
ProcyclidineProcyclidine may increase the anticholinergic activities of Tiotropium.Approved
PromazineThe metabolism of Tiotropium can be decreased when combined with Promazine.Approved, Vet Approved
PropanthelinePropantheline may increase the anticholinergic activities of Tiotropium.Approved
PropiverinePropiverine may increase the anticholinergic activities of Tiotropium.Investigational
PyridostigmineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Pyridostigmine.Approved
QuinethazoneThe serum concentration of Quinethazone can be increased when it is combined with Tiotropium.Approved
QuinidineQuinidine may increase the anticholinergic activities of Tiotropium.Approved
QuinineThe metabolism of Tiotropium can be decreased when combined with Quinine.Approved
RamosetronTiotropium may increase the constipating activities of Ramosetron.Approved
RanolazineThe metabolism of Tiotropium can be decreased when combined with Ranolazine.Approved, Investigational
RemifentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Remifentanil.Approved
RifabutinThe metabolism of Tiotropium can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Tiotropium can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Tiotropium can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Tiotropium can be decreased when combined with Ritonavir.Approved, Investigational
RivastigmineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Rivastigmine.Approved, Investigational
RolapitantThe metabolism of Tiotropium can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Tiotropium can be decreased when combined with Ropinirole.Approved, Investigational
SaquinavirThe metabolism of Tiotropium can be decreased when combined with Saquinavir.Approved, Investigational
ScopolamineScopolamine may increase the anticholinergic activities of Tiotropium.Approved
Scopolamine butylbromideScopolamine butylbromide may increase the anticholinergic activities of Tiotropium.Approved
SecretinThe therapeutic efficacy of Secretin can be decreased when used in combination with Tiotropium.Approved, Investigational
SertralineThe metabolism of Tiotropium can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Tiotropium can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Tiotropium can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Tiotropium can be increased when it is combined with Simeprevir.Approved
SolifenacinSolifenacin may increase the anticholinergic activities of Tiotropium.Approved
St. John's WortThe serum concentration of Tiotropium can be decreased when it is combined with St. John&#39;s Wort.Nutraceutical
StiripentolThe serum concentration of Tiotropium can be increased when it is combined with Stiripentol.Approved
SufentanilThe risk or severity of adverse effects can be increased when Tiotropium is combined with Sufentanil.Approved, Investigational
SulfisoxazoleThe metabolism of Tiotropium can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SulpirideThe therapeutic efficacy of Sulpiride can be decreased when used in combination with Tiotropium.Approved
TacrineThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Tacrine.Withdrawn
TapentadolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Tapentadol.Approved
TelaprevirThe metabolism of Tiotropium can be decreased when combined with Telaprevir.Approved
TelithromycinThe metabolism of Tiotropium can be decreased when combined with Telithromycin.Approved
TerbinafineThe metabolism of Tiotropium can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
ThioridazineThe metabolism of Tiotropium can be decreased when combined with Thioridazine.Approved
TiclopidineThe metabolism of Tiotropium can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Tiotropium can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Tiotropium can be decreased when it is combined with Tocilizumab.Approved
TolterodineTolterodine may increase the anticholinergic activities of Tiotropium.Approved, Investigational
TopiramateThe risk or severity of adverse effects can be increased when Tiotropium is combined with Topiramate.Approved
TramadolThe risk or severity of adverse effects can be increased when Tiotropium is combined with Tramadol.Approved, Investigational
TranylcypromineThe metabolism of Tiotropium can be decreased when combined with Tranylcypromine.Approved
TrichlorfonThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Trichlorfon.Vet Approved
TrichlormethiazideThe serum concentration of Trichlormethiazide can be increased when it is combined with Tiotropium.Approved, Vet Approved
TrihexyphenidylTrihexyphenidyl may increase the anticholinergic activities of Tiotropium.Approved
TrimethaphanTrimethaphan may increase the anticholinergic activities of Tiotropium.Approved
TropicamideTropicamide may increase the anticholinergic activities of Tiotropium.Approved
TrospiumTrospium may increase the anticholinergic activities of Tiotropium.Approved
TubocurarineTubocurarine may increase the anticholinergic activities of Tiotropium.Approved
UmeclidiniumUmeclidinium may increase the anticholinergic activities of Tiotropium.Approved
VecuroniumVecuronium may increase the anticholinergic activities of Tiotropium.Approved
VenlafaxineThe metabolism of Tiotropium can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Tiotropium can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Tiotropium can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Tiotropium can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot 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 CodesR03AL06R03BB04R03BB54
AHFS Codes
  • 12:08.08
PDB EntriesNot Available
FDA labelDownload (401 KB)
MSDSNot 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
SolutionRespiratory (inhalation)
CapsuleOral; Respiratory (inhalation)18 ug/1
CapsuleRespiratory (inhalation)18 mcg
SolutionRespiratory (inhalation)2.5 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
Taxonomy
ClassificationNot classified

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 ]
Comments
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Drug created on July 17, 2007 06:36 / Updated on December 03, 2016 02:47