Identification

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Name
Doxazosin
Accession Number
DB00590  (APRD00474)
Type
Small Molecule
Groups
Approved
Description

Doxazosin is an alpha-1 antagonist used for the treatment of benign prostatic hypertrophy (BPH) symptoms and hypertension. Other members of this drug class include Prazosin, Terazosin, Tamsulosin, and Alfuzosin.8 Because of its long-lasting effects, doxazosin can be administered once a day.5 It is marketed by Pfizer and was initially approved by the FDA in 1990.20

Structure
Thumb
Synonyms
  • 1-(4-Amino-6,7-dimethoxy-2-chinazolinyl)-4-(2,3-dihydro-1,4-benzodioxixin-2-ylcarbonyl)piperazin
  • 1-(4-Amino-6,7-Dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl)piperazin
  • Doxazosin
  • Doxazosina
  • Doxazosine
  • Doxazosinum
Product Ingredients
IngredientUNIICASInChI Key
Doxazosin mesylate86P6PQK0MU77883-43-3VJECBOKJABCYMF-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarduraTablet2 mg/1OralRoerig1990-11-02Not applicableUs
CarduraTablet1 mg/1OralPhysicians Total Care, Inc.1995-10-162012-06-30Us
CarduraTablet1 mg/1OralRoerig1990-11-02Not applicableUs
CarduraTablet8 mg/1OralPhysicians Total Care, Inc.1994-12-132012-06-30Us
CarduraTablet4 mg/1OralPhysicians Total Care, Inc.1993-06-222012-07-16Us
CarduraTablet8 mg/1OralRoerig1990-11-02Not applicableUs
CarduraTablet4 mg/1OralRoerig1990-11-02Not applicableUs
CarduraTablet2 mg/1OralPhysicians Total Care, Inc.1999-02-102012-06-30Us
Cardura XLTablet, multilayer, extended release8 mg/1OralRoerig2005-02-22Not applicableUs
Cardura XLTablet, multilayer, extended release4 mg/1OralRoerig2005-02-22Not applicableUs
Additional Data Available
  • Application Number
    Application Number

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

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  • Product Code
    Product Code

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

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-doxazosinTabletOralApotex Corporation1999-07-22Not applicableCanada
Apo-doxazosinTabletOralApotex Corporation1999-07-22Not applicableCanada
Apo-doxazosinTabletOralApotex Corporation1999-07-22Not applicableCanada
Dom-doxazosinTabletOralDominion Pharmacal2004-05-26Not applicableCanada
Dom-doxazosinTabletOralDominion Pharmacal2004-05-26Not applicableCanada
Dom-doxazosinTabletOralDominion Pharmacal2004-05-26Not applicableCanada
DoxazosinTablet2 mg/1OralA-S Medication Solutions2011-07-14Not applicableUs54569 516920180907 15195 1fnwg7c
DoxazosinTablet8 mg/1OralUnit Dose Services2000-10-202016-09-30Us50436 661920180907 15195 1kvhdbr
DoxazosinTablet1 mg/1OralPhysicians Total Care, Inc.2003-08-14Not applicableUs00378 4021 01 nlmimage10 934049c2
DoxazosinTablet4 mg/1OralPhysicians Total Care, Inc.2003-05-28Not applicableUs54868 480220180907 15195 85bilz
Additional Data Available
  • Application Number
    Application Number

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

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  • Product Code
    Product Code

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

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Cardura-1,2,and 4Doxazosin (1 mg) + Doxazosin (2 mg) + Doxazosin (4 mg)Kit; TabletOralAstra ZenecaNot applicableNot applicableCanada
Cardura-1,2,and 4Doxazosin (1 mg) + Doxazosin (2 mg) + Doxazosin (4 mg)Kit; TabletOralAstra ZenecaNot applicableNot applicableCanada
Cardura-1,2,and 4Doxazosin (1 mg) + Doxazosin (2 mg) + Doxazosin (4 mg)Kit; TabletOralAstra ZenecaNot applicableNot applicableCanada
International/Other Brands
Alfadil (Pfizer (Sweden)) / Cardenalin (Pfizer (Japan; discontinued)) / Cardular (Pfizer (Germany)) / Cardura-1 (Pfizer (Canada)) / Cardura-2 (Pfizer (Canada)) / Cardura-4 (Pfizer (Canada)) / Carduran (Pfizer (Brazil, Denmark, Norway, Spain)) / Diblocin (AstraZeneca (Germany)) / Normothen (Bioindustria (Italy)) / Supressin (Pfizer (Austria))
Categories
UNII
NW1291F1W8
CAS number
74191-85-8
Weight
Average: 451.4751
Monoisotopic: 451.185568935
Chemical Formula
C23H25N5O5
InChI Key
RUZYUOTYCVRMRZ-UHFFFAOYSA-N
InChI
InChI=1S/C23H25N5O5/c1-30-18-11-14-15(12-19(18)31-2)25-23(26-21(14)24)28-9-7-27(8-10-28)22(29)20-13-32-16-5-3-4-6-17(16)33-20/h3-6,11-12,20H,7-10,13H2,1-2H3,(H2,24,25,26)
IUPAC Name
2-[4-(2,3-dihydro-1,4-benzodioxine-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine
SMILES
COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N1CCN(CC1)C(=O)C1COC2=CC=CC=C2O1

Pharmacology

Indication

Doxazosin is indicated to treat the symptoms of benign prostatic hypertrophy, which may include urinary frequency, urgency, and nocturia, among other symptoms. In addition, doxazosin is indicated alone or in combination with various antihypertensive agents for the management of hypertension.19 Off-label uses of doxazosin include the treatment of pediatric hypertension2 and the treatment of ureteric calculi.3

Associated Conditions
Pharmacodynamics

Doxazosin decreases standing and supine blood pressure5 and relieves the symptoms of benign prostatic hypertrophy through the inhibition of alpha-1 receptors. Doxazosin may cause hypotension due to its pharmacological actions. This frequently occurs in the upright position, leading to a feeling of dizziness or lightheadedness. The first dose of doxazosin may lead to such effects, however, subsequent doses may also cause them. The risk of these effects is particularly high when dose adjustments occur or there are long intervals between doxazosin doses. Treatment should be started with the 1 mg dose of doxazosin, followed by slow titration to the appropriate dose.19 Patients must be advised of this risk and to avoid situations in which syncope and dizziness could be hazardous following the ingestion of doxazosin.19 Interestingly doxazosin exerts beneficial effects on plasma lipids. It reduces LDL (low-density lipoprotein) cholesterol and triglyceride levels and increases HDL (high-density lipoprotein) cholesterol levels.5

A note on priapism risk

In rare cases, doxazosin and other alpha-1 blockers may cause priapism, a painful occurrence of persistent and unrelievable penile erection that can lead to impotence if medical attention is not sought as soon as possible. Patients must be advised of the priapism risk associated with doxazosin and to seek medical attention immediately if it is suspected.9,19

Mechanism of action

Doxazosin selectively inhibits the postsynaptic alpha-1 receptors on vascular smooth muscle by nonselectively blocking the alpha-1a, alpha-1b, and alpha-1d subtypes12,13. This action on blood vessels decreases systemic peripheral vascular resistance, reducing blood pressure, exerting minimal effects on the heart rate due to its receptor selectivity.5,10 Norepinephrine-activated alpha-1 receptors located on the prostate gland and bladder neck normally cause contraction of regional muscular tissue, obstructing urinary flow and contributing to the symptoms of benign prostatic hypertrophy. Alpha-1 antagonism causes smooth muscle relaxation in the prostate and bladder, effectively relieving urinary frequency, urgency, weak urinary stream, and other unpleasant effects of BPH.6 Recently, doxazosin was found to cause apoptosis of hERG potassium channels in an in vitro setting, possibly contributing to a risk of heart failure with doxazosin use.14,15,16

TargetActionsOrganism
AAlpha-1A adrenergic receptor
antagonist
Humans
AAlpha-1D adrenergic receptor
antagonist
Humans
UHERG human cardiac K+ channel
inhibitor
Humans
UAlpha-1B adrenergic receptorNot AvailableHumans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Doxazosin is rapidly absorbed in the gastrointestinal tract and peak concentrations are achieved within 2-3 hours after administration.11 The bioavailability is about 60%-70%.7,19 The intake of food with doxazosin is not expected to cause clinically significant effects.19

Volume of distribution

The volume of distribution of doxazosin is 1.0-1.9 L/kg.7,11 In a study of radiolabeled doxazosin administered to pregnant rats, doxazosin was found to cross the placenta.19

Protein binding

The plasma protein binding of doxazosin is estimated at 98%.4,19. It has also been shown to be bound to the alpha-1 acid glycoprotein.18

Metabolism

Hepatic metabolism of doxazosin produces inactive O-demethylated and C-hydroxylated metabolites. Metabolism occurs via O-demethylation of the quinazoline nucleus of doxazosin or via hydroxylation of its benzodioxan portion.19 The enzymes involved in the metabolism of doxazosin include CYP2C1923, CYP2D6, CYP2C19, and CYP3A4, which is the primary metabolizing enzyme.22 Doxazosin itself is considered to be mainly responsible for its pharmacological action7, however, some active metabolites have been identified whose pharmacokinetics have not been adequately characterized.19

Route of elimination

In a pharmacokinetic study using a 1 mg IV radiolabeled dose and a 2 mg oral dose, 63% of the ingested doxazosin was found to be excreted in the feces and about 9% of the dose was found to be excreted in the urine.7,19 Traces of radiolabeled unchanged drug were found in the urine and about 5% of the administered drug was found as unchanged drug excreted in the feces.19

Half life

The terminal elimination half-life of doxazosin has been estimated at 9-12 hours according to some resources.4,7 The FDA label indicates the elimination half-life of doxazosin is 22 hours.19

Clearance

The clearance of doxazosin is low and ranges from approximately 1-2 ml/min/kg.4,11

Toxicity

LD50 information

The oral LD50 of doxazosin in mice is >1000 mg/kg.21

Overdose information

Symptoms of overdose include hypotension, changes in heart rate, and drowsiness.10 Administer supportive treatment in case of an overdose with doxazosin. Remove unabsorbed doxazosin from the gastrointestinal tract, correct hypotension, and closely monitor vital signs.10

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Doxazosin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Doxazosin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid may decrease the antihypertensive activities of Doxazosin.
1-benzylimidazole1-benzylimidazole may decrease the antihypertensive activities of Doxazosin.
2,5-Dimethoxy-4-ethylamphetamineThe therapeutic efficacy of Doxazosin can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe therapeutic efficacy of Doxazosin can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Doxazosin.
4-Bromo-2,5-dimethoxyamphetamineThe therapeutic efficacy of Doxazosin can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
4-Bromo-2,5-dimethoxyphenethylamineThe therapeutic efficacy of 4-Bromo-2,5-dimethoxyphenethylamine can be decreased when used in combination with Doxazosin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Doxazosin.
Additional Data Available
  • Extended Description
    Extended Description

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

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  • Severity
    Severity

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

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  • Evidence Level
    Evidence Level

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

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  • Action
    Action

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Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Take without regard to meals.

References

Synthesis Reference

K. S. Keshava Murthy, Gamini Weeratunga, Tianhao Zhou, Bhaskar Reddy Guntoori, "Process for the manufacture of intermediates suitable to make doxazosin, terazosin, prazosin, tiodazosin and related antihypertensive medicines." U.S. Patent US5919931, issued September, 1986.

US5919931
General References
  1. Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM: Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404. [PubMed:12461301]
  2. Rao G: Diagnosis, Epidemiology, and Management of Hypertension in Children. Pediatrics. 2016 Aug;138(2). pii: peds.2015-3616. doi: 10.1542/peds.2015-3616. Epub 2016 Jul 12. [PubMed:27405770]
  3. Liatsikos EN, Katsakiori PF, Assimakopoulos K, Voudoukis T, Kallidonis P, Constantinides C, Athanasopoulos A, Stolzenburg JU, Perimenis P: Doxazosin for the management of distal-ureteral stones. J Endourol. 2007 May;21(5):538-41. doi: 10.1089/end.2006.0107. [PubMed:17523910]
  4. Kaye B, Cussans NJ, Faulkner JK, Stopher DA, Reid JL: The metabolism and kinetics of doxazosin in man, mouse, rat and dog. Br J Clin Pharmacol. 1986;21 Suppl 1:19S-25S. doi: 10.1111/j.1365-2125.1986.tb02849.x. [PubMed:2939865]
  5. Young RA, Brogden RN: Doxazosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in mild or moderate hypertension. Drugs. 1988 May;35(5):525-41. doi: 10.2165/00003495-198835050-00003. [PubMed:2899495]
  6. Doggrell SA: After ALLHAT: doxazosin for the treatment of benign prostatic hyperplasia. Expert Opin Pharmacother. 2004 Sep;5(9):1957-64. doi: 10.1517/14656566.5.9.1957 . [PubMed:15330733]
  7. Elliott HL, Meredith PA, Reid JL: Pharmacokinetic overview of doxazosin. Am J Cardiol. 1987 May 29;59(14):78G-81G. doi: 10.1016/0002-9149(87)90162-7. [PubMed:2884857]
  8. Kaplan SA: alpha-Blocker Therapy: Current Update. Rev Urol. 2005;7 Suppl 8:S34-42. [PubMed:16985889]
  9. Pahuja A, Bashir J, Williamson EM, Barber N: Unresolved priapism secondary to tamsulosin. Int J Impot Res. 2005 May-Jun;17(3):293-4. doi: 10.1038/sj.ijir.3901281. [PubMed:15549140]
  10. Satar S, Sebe A, Avci A, Yesilagac H, Gokel Y: Acute intoxication with doxazosin. Hum Exp Toxicol. 2005 Jun;24(6):337-9. doi: 10.1191/0960327105ht531oa. [PubMed:16004202]
  11. Cubeddu LX, Fuenmayor N, Caplan N, Ferry D: Clinical pharmacology of doxazosin in patients with essential hypertension. Clin Pharmacol Ther. 1987 Apr;41(4):439-49. doi: 10.1038/clpt.1987.54. [PubMed:2951051]
  12. Schwinn DA, Roehrborn CG: Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008 Mar;15(3):193-9. doi: 10.1111/j.1442-2042.2007.01956.x. [PubMed:18304211]
  13. Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997 Jul;282(1):228-35. [PubMed:9223558]
  14. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. [PubMed:15098086]
  15. Thomas D, Bloehs R, Koschny R, Ficker E, Sykora J, Kiehn J, Schlomer K, Gierten J, Kathofer S, Zitron E, Scholz EP, Kiesecker C, Katus HA, Karle CA: Doxazosin induces apoptosis of cells expressing hERG K+ channels. Eur J Pharmacol. 2008 Jan 28;579(1-3):98-103. doi: 10.1016/j.ejphar.2007.10.051. Epub 2007 Dec 4. [PubMed:18054910]
  16. Jehle J, Schweizer PA, Katus HA, Thomas D: Novel roles for hERG K(+) channels in cell proliferation and apoptosis. Cell Death Dis. 2011 Aug 18;2:e193. doi: 10.1038/cddis.2011.77. [PubMed:21850047]
  17. Hammond KP, Nielsen C, Linnebur SA, Langness JA, Ray G, Maroni P, Kiser JJ: Priapism induced by boceprevir-CYP3A4 inhibition and alpha-adrenergic blockade: case report. Clin Infect Dis. 2014 Jan;58(1):e35-8. doi: 10.1093/cid/cit673. Epub 2013 Oct 2. [PubMed:24092799]
  18. Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. doi: 10.1002/jps.2600750208. [PubMed:2870173]
  19. Doxazosin FDA label [Link]
  20. FDA approval package, Cardura [Link]
  21. MSDS, Pfizer [Link]
  22. Cardura XL label [Link]
  23. Cardura monograph [Link]
External Links
Human Metabolome Database
HMDB0014728
KEGG Drug
D07874
KEGG Compound
C06970
PubChem Compound
3157
PubChem Substance
46506825
ChemSpider
3045
BindingDB
86731
ChEBI
4708
ChEMBL
CHEMBL707
Therapeutic Targets Database
DAP000381
PharmGKB
PA449407
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Doxazosin
ATC Codes
C02CA04 — Doxazosin
AHFS Codes
  • 24:20.00 — Alpha-adrenergic Blocking Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableCocaine Abuse / Dependence, Cocaine / Substance Abuse1
1CompletedNot AvailableSubstance-Related Disorders1
1CompletedBasic ScienceAmphetamine-Related Disorders / Moods Disorders / Substance-Related Disorders1
1CompletedTreatmentDependence, Cocaine1
1CompletedTreatmentErectile Dysfunction (ED)1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1Not Yet RecruitingOtherAlcohol Use Disorder (AUD)1
1RecruitingTreatmentAllogeneic Hematopoietic Stem Cell Transplant Recipient / Allogeneic Hematopoietic Stem Cell Transplantation Recipient / Blasts Under 5 Percent of Bone Marrow Nucleated Cells / IDH2 Gene Mutation / Leukemia Acute Myeloid Leukemia (AML) / Myeloid leukaemia in remission1
1RecruitingTreatmentDependence, Cocaine1
1RecruitingTreatmentPost Traumatic Stress Disorder (PTSD)1
1, 2Active Not RecruitingTreatmentAlcohol Use Disorder (AUD) / Post Traumatic Stress Disorder (PTSD)1
1, 2CompletedTreatmentMethamphetamine or Cocaine Dependence1
2Active Not RecruitingTreatmentAlcohol Use Disorders (AUD) / Post Traumatic Stress Disorder (PTSD) / Posttraumatic Stress Disorders1
2CompletedDiagnosticDependence, Cocaine1
2CompletedTreatmentAlcohol Dependence / Anxiety1
2CompletedTreatmentBenign Prostatic Hyperplasia (BPH)1
2CompletedTreatmentCardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension) / Vascular Diseases1
2CompletedTreatmentDependence, Cocaine1
2CompletedTreatmentSmoking1
2Not Yet RecruitingTreatmentAcute, recurrent Myeloid Leukemia / Blasts 5 Percent or More of Bone Marrow Nucleated Cells / IDH2 Gene Mutation1
2RecruitingTreatmentAcute Bilineal Leukemia / Acute Biphenotypic Leukemia (ABL) / Acute, recurrent Myeloid Leukemia / Chronic Myelomonocytic Leukemia / IDH2 Gene Mutation / Myelodysplastic Syndrome / Refractory Acute Myeloid Leukemia1
2RecruitingTreatmentAlcohol Dependence1
2RecruitingTreatmentPost Traumatic Stress Disorder (PTSD)1
2, 3RecruitingTreatmentHigh Blood Pressure (Hypertension)1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / Heart Diseases / Heart Failure / High Blood Pressure (Hypertension) / High Cholesterol / Myocardial Infarction / Myocardial Ischemia1
3CompletedTreatmentProstatic Hyperplasia / Prostatic Hypertrophy, Benign1
3RecruitingTreatmentParaganglioma / Pheochromocytomas1
3Unknown StatusTreatmentRenal Stones1
4Active Not RecruitingTreatmentHypertension, Resistant to Conventional Therapy1
4CompletedBasic ScienceIdiopathic Dilated Cardiomyopathy1
4CompletedTreatmentAllergic Rhinitis (AR)1
4CompletedTreatmentBladder Outlet Obstruction1
4CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Strokes1
4CompletedTreatmentDiabetes Mellitus (DM) / Hypertension,Essential / Renal Failure1
4CompletedTreatmentHigh Blood Pressure (Hypertension)6
4CompletedTreatmentPheochromocytomas1
4CompletedTreatmentPost Traumatic Stress Disorder (PTSD)1
4CompletedTreatmentProstate1
4Unknown StatusPreventionDiabetic Nephropathies1
4Unknown StatusTreatmentBenign Prostatic Hyperplasia (BPH) / Urinary Bladder, Overactive1
4WithdrawnTreatmentBenign Prostatic Hyperplasia (BPH)1
Not AvailableCompletedNot AvailableBenign Prostatic Hyperplasia (BPH)1
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / High Blood Pressure (Hypertension) / Myocardial Infarction1
Not AvailableCompletedNot AvailableProstatic Hyperplasia3
Not AvailableCompletedBasic ScienceBenign Prostatic Hyperplasia (BPH)1
Not AvailableTerminatedTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableTerminatedTreatmentHigh Blood Pressure (Hypertension) / Microvascular Angina1
Not AvailableTerminatedTreatmentProstatic Hyperplasia / Urinary Retention1

Pharmacoeconomics

Manufacturers
  • Pfizer inc
  • Pfizer laboratories div pfizer inc
  • Actavis elizabeth llc
  • Apotex inc
  • Dava pharmaceuticals inc
  • Genpharm inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Kv pharmaceutical co
  • Mylan pharmaceuticals inc
  • Pliva inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Cardinal Health
  • DAVA Pharmaceuticals
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • General Injectables and Vaccines Inc.
  • Golden State Medical Supply Inc.
  • Heartland Repack Services LLC
  • International Laboratories Inc.
  • Ivax Pharmaceuticals
  • Legacy Pharmaceuticals Packaging LLC
  • Major Pharmaceuticals
  • Merrell Pharmaceuticals Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Patheon Inc.
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Redpharm Drug
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • US Pharmaceutical Group
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
Tablet, multilayer, extended releaseOral4 mg/1
Tablet, multilayer, extended releaseOral8 mg/1
TabletOral
Kit; tabletOral
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral4 mg/1
TabletOral8 mg/1
Prices
Unit descriptionCostUnit
Cardura XL 4 mg 24 Hour tablet2.22USD tablet
Cardura xl 8 mg tablet2.04USD tablet
Cardura xl 4 mg tablet1.94USD tablet
Cardura 8 mg tablet1.93USD tablet
Cardura 4 mg tablet1.89USD tablet
Cardura 2 mg tablet1.81USD tablet
Cardura 1 mg tablet1.72USD tablet
Doxazosin mesylate 8 mg tablet1.04USD tablet
Cardura 4 mg Tablet1.0USD tablet
Doxazosin mesylate 4 mg tablet0.99USD tablet
Doxazosin mesylate 1 mg tablet0.94USD tablet
Doxazosin mesylate 2 mg tablet0.94USD tablet
Cardura 2 mg Tablet0.77USD tablet
Cardura 1 mg Tablet0.64USD tablet
Apo-Doxazosin 4 mg Tablet0.56USD tablet
Mylan-Doxazosin 4 mg Tablet0.56USD tablet
Novo-Doxazosin 4 mg Tablet0.56USD tablet
Pms-Doxazosin 4 mg Tablet0.56USD tablet
Apo-Doxazosin 2 mg Tablet0.43USD tablet
Mylan-Doxazosin 2 mg Tablet0.43USD tablet
Novo-Doxazosin 2 mg Tablet0.43USD tablet
Pms-Doxazosin 2 mg Tablet0.43USD tablet
Apo-Doxazosin 1 mg Tablet0.36USD tablet
Mylan-Doxazosin 1 mg Tablet0.36USD tablet
Novo-Doxazosin 1 mg Tablet0.36USD tablet
Pms-Doxazosin 1 mg Tablet0.36USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)275-277https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3285710.htm
boiling point (°C)718https://www.scbt.com/scbt/product/doxazosin-mesylate-77883-43-3
water solubility0.8%https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019668s021lbl.pdf
logP2.1https://pubchem.ncbi.nlm.nih.gov/compound/Doxazosin
pKa6.52https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL707/
Predicted Properties
PropertyValueSource
Water Solubility0.79 mg/mLALOGPS
logP2.53ALOGPS
logP2.14ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)12.67ChemAxon
pKa (Strongest Basic)7.24ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area112.27 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity121.64 m3·mol-1ChemAxon
Polarizability47.17 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9627
Caco-2 permeable+0.7863
P-glycoprotein substrateSubstrate0.7303
P-glycoprotein inhibitor INon-inhibitor0.7391
P-glycoprotein inhibitor IINon-inhibitor0.9528
Renal organic cation transporterNon-inhibitor0.6909
CYP450 2C9 substrateNon-substrate0.9011
CYP450 2D6 substrateNon-substrate0.8195
CYP450 3A4 substrateSubstrate0.7228
CYP450 1A2 substrateNon-inhibitor0.8293
CYP450 2C9 inhibitorNon-inhibitor0.9161
CYP450 2D6 inhibitorNon-inhibitor0.9533
CYP450 2C19 inhibitorNon-inhibitor0.9084
CYP450 3A4 inhibitorNon-inhibitor0.8002
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9078
Ames testNon AMES toxic0.5648
CarcinogenicityNon-carcinogens0.8905
BiodegradationNot ready biodegradable0.9854
Rat acute toxicity2.1954 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8602
hERG inhibition (predictor II)Inhibitor0.823
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0010900000-9601aa919c95799ec009
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0kei-0981100000-a9ee3121ba6832366f8e
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0970000000-5261f1bc60ceee4364de
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0950000000-f649236044e4e2a5de38
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-1920000000-86655cc3bb892d757068
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-1900000000-88bca2ddf2930fa0c468
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0000900000-449254642300c1324285
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0002900000-3097c8a3403b52610918
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0079100000-06d36a9b7afe6cf0c6e9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000t-1091000000-cbd9b2106818ef5fd2ba
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-1190000000-a1c84b0c3657d8000e35
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-1390000000-e802cb93ca8d6934ee96

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
N-arylpiperazines
Alternative Parents
Quinazolinamines / Benzo-1,4-dioxanes / Anisoles / Dialkylarylamines / Alkyl aryl ethers / Aminopyrimidines and derivatives / Para dioxins / Imidolactams / Tertiary carboxylic acid amides / Heteroaromatic compounds
show 8 more
Substituents
N-arylpiperazine / Quinazolinamine / Diazanaphthalene / Benzo-1,4-dioxane / Benzodioxane / Quinazoline / Anisole / Dialkylarylamine / Alkyl aryl ether / Aminopyrimidine
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, monocarboxylic acid amide, aromatic amine, quinazolines, benzodioxine, N-acylpiperazine (CHEBI:4708)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Yono M, Foster HE Jr, Shin D, Takahashi W, Pouresmail M, Latifpour J: Doxazosin-induced up-regulation of alpha 1A-adrenoceptor mRNA in the rat lower urinary tract. Can J Physiol Pharmacol. 2004 Oct;82(10):872-8. [PubMed:15573147]
  2. Michel MC, Grubbel B, Taguchi K, Verfurth F, Otto T, Kropfl D: Drugs for treatment of benign prostatic hyperplasia: affinity comparison at cloned alpha 1-adrenoceptor subtypes and in human prostate. J Auton Pharmacol. 1996 Feb;16(1):21-8. [PubMed:8736427]
  3. Roehrborn CG, Schwinn DA: Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol. 2004 Mar;171(3):1029-35. [PubMed:14767264]
  4. Ishizuka O, Pandita RK, Mattiasson A, Steers WD, Andersson KE: Stimulation of bladder activity by volume, L-dopa and capsaicin in normal conscious rats--effects of spinal alpha 1-adrenoceptor blockade. Naunyn Schmiedebergs Arch Pharmacol. 1997 Jun;355(6):787-93. [PubMed:9205965]
  5. Bae JH, Jung PB, Lee JG: The effects of alpha-adrenoceptor antagonists on the urethral perfusion pressure of the female rat. BJU Int. 2005 Nov;96(7):1131-5. [PubMed:16225542]
  6. Greco KA, McVary KT: The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43. doi: 10.1038/ijir.2008.51. [PubMed:19002123]
  7. Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [PubMed:17070143]
  8. Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [PubMed:10393471]
  9. Schwinn DA, Roehrborn CG: Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008 Mar;15(3):193-9. doi: 10.1111/j.1442-2042.2007.01956.x. [PubMed:18304211]
  10. Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997 Jul;282(1):228-35. [PubMed:9223558]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997 Jul;282(1):228-35. [PubMed:9223558]
  2. Schwinn DA, Roehrborn CG: Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008 Mar;15(3):193-9. doi: 10.1111/j.1442-2042.2007.01956.x. [PubMed:18304211]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This is a potential target action of doxazosin that was demonstrated by in vitro studies.
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...

Components:
References
  1. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. [PubMed:15098086]
  2. Thomas D, Bloehs R, Koschny R, Ficker E, Sykora J, Kiehn J, Schlomer K, Gierten J, Kathofer S, Zitron E, Scholz EP, Kiesecker C, Katus HA, Karle CA: Doxazosin induces apoptosis of cells expressing hERG K+ channels. Eur J Pharmacol. 2008 Jan 28;579(1-3):98-103. doi: 10.1016/j.ejphar.2007.10.051. Epub 2007 Dec 4. [PubMed:18054910]
  3. Jehle J, Schweizer PA, Katus HA, Thomas D: Novel roles for hERG K(+) channels in cell proliferation and apoptosis. Cell Death Dis. 2011 Aug 18;2:e193. doi: 10.1038/cddis.2011.77. [PubMed:21850047]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Schwinn DA, Roehrborn CG: Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008 Mar;15(3):193-9. doi: 10.1111/j.1442-2042.2007.01956.x. [PubMed:18304211]
  2. Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997 Jul;282(1):228-35. [PubMed:9223558]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Hammond KP, Nielsen C, Linnebur SA, Langness JA, Ray G, Maroni P, Kiser JJ: Priapism induced by boceprevir-CYP3A4 inhibition and alpha-adrenergic blockade: case report. Clin Infect Dis. 2014 Jan;58(1):e35-8. doi: 10.1093/cid/cit673. Epub 2013 Oct 2. [PubMed:24092799]
  2. Cardura XL label [Link]
Kind
Protein
Organism
Humans
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Hammond KP, Nielsen C, Linnebur SA, Langness JA, Ray G, Maroni P, Kiser JJ: Priapism induced by boceprevir-CYP3A4 inhibition and alpha-adrenergic blockade: case report. Clin Infect Dis. 2014 Jan;58(1):e35-8. doi: 10.1093/cid/cit673. Epub 2013 Oct 2. [PubMed:24092799]
  2. Cardura XL label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Hammond KP, Nielsen C, Linnebur SA, Langness JA, Ray G, Maroni P, Kiser JJ: Priapism induced by boceprevir-CYP3A4 inhibition and alpha-adrenergic blockade: case report. Clin Infect Dis. 2014 Jan;58(1):e35-8. doi: 10.1093/cid/cit673. Epub 2013 Oct 2. [PubMed:24092799]
  2. Dailymed [Link]
  3. Cardura XL label [Link]
  4. Cardura monograph [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Cardura monograph [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This transporter action is supported by in vitro data only.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [PubMed:11895100]
  2. Takara K, Sakaeda T, Kakumoto M, Tanigawara Y, Kobayashi H, Okumura K, Ohnishi N, Yokoyama T: Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport. Oncol Res. 2009;17(11-12):527-33. [PubMed:19806783]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Stage TB, Brosen K, Christensen MM: A Comprehensive Review of Drug-Drug Interactions with Metformin. Clin Pharmacokinet. 2015 Aug;54(8):811-24. doi: 10.1007/s40262-015-0270-6. [PubMed:25943187]
  2. Dujic T, Zhou K, Donnelly LA, Tavendale R, Palmer CN, Pearson ER: Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. Diabetes. 2015 May;64(5):1786-93. doi: 10.2337/db14-1388. Epub 2014 Dec 15. [PubMed:25510240]

Drug created on June 13, 2005 07:24 / Updated on September 17, 2019 03:38