Identification

Name
Fondaparinux
Accession Number
DB00569  (APRD00500, DB11728)
Type
Small Molecule
Groups
Approved, Investigational
Description

Fondaparinux (Arixtra) is a synthetic pentasaccharide anticoagulant. Apart from the O-methyl group at the reducing end of the molecule, the identity and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units that can be isolated after either chemical or enzymatic cleavage of the polymeric glycosaminoglycan heparin and heparan sulfate (HS). This monomeric sequence in heparin and HS is thought to form the high affinity binding site for the natural anti-coagulant factor, antithrombin III (ATIII). Binding of heparin/HS to ATIII has been shown to increase the anti-coagulant activity of antithrombin III 1000-fold. Fondaparinux potentiates the neutralizing action of ATIII on activated Factor X 300-fold. Fondaparinux may be used: to prevent venous thromboembolism in patients who have undergone orthopedic surgery of the lower limbs (e.g. hip fracture, hip replacement and knee surgery); to prevent VTE in patients undergoing abdominal surgery who are are at high risk of thromboembolic complications; in the treatment of deep vein thrombosis (DVT) and pumonary embolism (PE); in the management of unstable angina (UA) and non-ST segment elevation myocardial infarction (NSTEMI); and in the management of ST segment elevation myocardial infarction (STEMI).

Structure
Thumb
Synonyms
  • Natural heparin pentasaccharide
Product Ingredients
IngredientUNIICASInChI Key
Fondaparinux sodiumX0Q6N9USOZ114870-03-0XEKSTYNIJLDDAZ-JASSWCPGSA-D
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ArixtraInjection, solution7.5 mg/0.6mlSubcutaneousAspen Pharma Trading Limited2002-03-21Not applicableEu
ArixtraInjection, solution1.5 mg/0.3mlSubcutaneousAspen Pharma Trading Limited2002-03-21Not applicableEu
ArixtraSolution10 mgSubcutaneousAspen Pharmacare Canada Inc.2008-04-17Not applicableCanada
ArixtraSolution2.5 mgIntravenous; SubcutaneousAspen Pharmacare Canada Inc.2002-07-19Not applicableCanada
ArixtraInjection, solution5 mg/0.4mlSubcutaneousAspen Pharma Trading Limited2002-03-21Not applicableEu
ArixtraInjection, solution2.5 mg/0.5mlIntravenous; SubcutaneousAspen Pharma Trading Limited2002-03-21Not applicableEu
ArixtraInjection, solution2.5 mg/0.5mlIntravenous; SubcutaneousAspen Pharma Trading Limited2002-03-21Not applicableEu
ArixtraInjection, solution7.5 mg/0.6mlSubcutaneousAspen Pharma Trading Limited2002-03-21Not applicableEu
ArixtraInjection, solution1.5 mg/0.3mlSubcutaneousAspen Pharma Trading Limited2002-03-21Not applicableEu
ArixtraInjection, solution5 mg/0.4mlSubcutaneousAspen Pharma Trading Limited2002-03-21Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fondaparinux SodiumInjection10 mg/0.8mLSubcutaneousDr Reddy's Laboratories2011-07-14Not applicableUs
Fondaparinux SodiumInjection, solution2.5 mg/0.5mLSubcutaneousMylan Institutional LLC2015-01-05Not applicableUs
Fondaparinux SodiumInjection5 mg/0.4mLSubcutaneousSandoz2018-06-18Not applicableUs
Fondaparinux SodiumInjection2.5 mg/0.5mLSubcutaneousDr Reddy's Laboratories2011-07-14Not applicableUs
Fondaparinux SodiumInjection, solution10 mg/0.8mLSubcutaneousAuro Medics Pharma Llc2017-12-26Not applicableUs
Fondaparinux SodiumInjection, solution2.5 mg/0.5mLSubcutaneousAuro Medics Pharma Llc2017-12-26Not applicableUs
Fondaparinux SodiumInjection, solution7.5 mg/0.6mLSubcutaneousMylan Institutional LLC2015-01-05Not applicableUs
Fondaparinux SodiumInjection5 mg/0.4mLSubcutaneousDr Reddy's Laboratories2017-07-27Not applicableUs
Fondaparinux SodiumInjection7.5 mg/0.6mLSubcutaneousDr Reddy's Laboratories2011-07-14Not applicableUs
Fondaparinux SodiumInjection10 mg/0.8mLSubcutaneousSandoz2018-06-18Not applicableUs
International/Other Brands
Arixtra
Categories
UNII
J177FOW5JL
CAS number
104993-28-4
Weight
Average: 1508.263
Monoisotopic: 1506.951330709
Chemical Formula
C31H53N3O49S8
InChI Key
KANJSNBRCNMZMV-ABRZTLGGSA-N
InChI
InChI=1S/C31H53N3O49S8/c1-69-27-9(33-85(48,49)50)13(37)17(6(74-27)3-71-88(57,58)59)76-31-22(83-91(66,67)68)16(40)21(24(81-31)26(43)44)79-29-10(34-86(51,52)53)19(82-90(63,64)65)18(7(75-29)4-72-89(60,61)62)77-30-15(39)14(38)20(23(80-30)25(41)42)78-28-8(32-84(45,46)47)12(36)11(35)5(73-28)2-70-87(54,55)56/h5-24,27-40H,2-4H2,1H3,(H,41,42)(H,43,44)(H,45,46,47)(H,48,49,50)(H,51,52,53)(H,54,55,56)(H,57,58,59)(H,60,61,62)(H,63,64,65)(H,66,67,68)/t5-,6-,7-,8-,9-,10-,11-,12-,13-,14-,15-,16+,17-,18-,19-,20+,21+,22-,23+,24-,27+,28-,29-,30-,31-/m1/s1
IUPAC Name
(2R,3S,4S,5R,6R)-3-{[(2R,3R,4R,5R,6R)-5-{[(2R,3R,4R,5S,6S)-6-carboxy-5-{[(2R,3R,4R,5S,6R)-4,5-dihydroxy-3-(sulfoamino)-6-[(sulfooxy)methyl]oxan-2-yl]oxy}-3,4-dihydroxyoxan-2-yl]oxy}-3-(sulfoamino)-4-(sulfooxy)-6-[(sulfooxy)methyl]oxan-2-yl]oxy}-4-hydroxy-6-{[(2R,3S,4R,5R,6S)-4-hydroxy-6-methoxy-5-(sulfoamino)-2-[(sulfooxy)methyl]oxan-3-yl]oxy}-5-(sulfooxy)oxane-2-carboxylic acid
SMILES
CO[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](O[C@@H]2O[C@H]([C@@H](O[C@H]3O[C@H](COS(O)(=O)=O)[C@@H](O[C@@H]4O[C@@H]([C@@H](O[C@H]5O[C@H](COS(O)(=O)=O)[C@@H](O)[C@H](O)[C@H]5NS(O)(=O)=O)[C@H](O)[C@H]4O)C(O)=O)[C@H](OS(O)(=O)=O)[C@H]3NS(O)(=O)=O)[C@H](O)[C@H]2OS(O)(=O)=O)C(O)=O)[C@H](O)[C@H]1NS(O)(=O)=O

Pharmacology

Indication

Approved for: (1) prophylaxis of VTE for up to one month post surgery in patients undergoing orthopedic surgery of the lower limbs such as hip fracture, hip replacement and knee surgery; (2) prophylaxis of VTE patients undergoing abdominal surgery who are at high risk of thromboembolic complications (e.g. patients undergoing abdominal cancer surgery); (3) treatment of acute DVT and PE; (4) management of UA and NSTEMI for the prevention of death and subsequent myocardial infarction (MI); and (5) management of STEMI for the prevention of death and myocardial reinfarction in patients who are managed with thrombolytics or who are initially to receive no form of reperfusion therapy. Fondaparinux should not be used as the sole anticoagulant during percutaneous coronary intervention (PCI) due to an increased risk of guiding catheter thrombosis.

Associated Conditions
Pharmacodynamics

Fondaparinux binds specifically to the natural anticoagulant factor, ATIII. Binding to ATIII potentiates the neutralizing action of ATIII on Factor Xa 300-times. Neutralization of Factor Xa decreases the conversion of prothrombin to thrombin, which subsequently decreases the conversion of fibrinogen to fibrin (loose meshwork). The decrease in thrombin also decreases the activation of Factor XIII, which decreases the conversion of fibrin in its loose meshwork form to its stabilized meshwork form. Disruption of the coagulation cascade effectively decreases the formation of blood clots. Fondaparinux does not inactivate thrombin (activated Factor II). According to the manufacturer, fondaparinux has no known effect on platelet function. In studies comparing fondaparinux to enoxaparin, decreases in platelet levels were observed in similar numbers of patients from both groups (2-5%) [1, 2]. At the recommended dose, Fondaparinux does not affect fibrinolytic activity or bleeding time. There is no antidote for fondaparinux. Monitoring of the anticoagulant activity of fondaparinux is not generally required. The anti-factor Xa assay may be used to monitor therapy in special populations such as those with renal impairment or who are pregnant. Complete blood count (CBC) and kidney function should be monitored during treatment.

Mechanism of action

The antithrombotic activity of fondaparinux is the result of ATIII-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, Fondaparinux potentiates (about 300 times) the neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. It is thought that fondaparinux is unlikely to induce thrombocytopenia via a heparin-induced thrombocytopenia (HIT)-like mechanism given its chemical structure [22]. As a result, fondaparinux has been used as an alternative anticoagulant in heparin-induced thrombocytopenia (HIT) patients [23, 24, 25]. However, it is important to note that rare cases of HIT have been reported in patients treated with fondaparinux [26, 27].

TargetActionsOrganism
AAntithrombin-III
potentiator
Human
ACoagulation factor X
inhibitor
Human
Absorption

100% bioavailability when administered subcutaneously

Volume of distribution
  • 7 - 11 L (healthy adults), distributed primarily in blood
Protein binding

94% in vitro protein binding specifically to ATIII

Metabolism

Not metabolized

Route of elimination

In individuals with normal kidney function, fondaparinux is eliminated in urine mainly as unchanged drug.

Half life

17-21 hours

Clearance
Not Available
Toxicity

As with other anticoagulants, the main concern is increased bleed risk. The risk of hemorrhage may increase with decreased renal function, body mass less than 50 kg, and moderate to severe hepatic function.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Fondaparinux Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Fondaparinux can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinThe risk or severity of bleeding can be increased when Fondaparinux is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Fondaparinux is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Fondaparinux can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Fondaparinux can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Fondaparinux is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Fondaparinux can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Fondaparinux can be increased when used in combination with 5beta-dihydrotestosterone.
AbacavirFondaparinux may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Fondaparinux.
Food Interactions
Not Available

References

Synthesis Reference

Jean-Francois Branellec, Christian Morello, Pierre Potier, Patrick Trouilleux, Petrus Marcus Bastiaansen, Henricus Cornelis Claassen, "Highly pure fondaparinux sodium composition, process for preparing said composition and pharmaceutical compositions containing it as active principle." U.S. Patent US20050020536, issued January 27, 2005.

US20050020536
General References
  1. Eriksson BI, Bauer KA, Lassen MR, Turpie AG: Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 2001 Nov 1;345(18):1298-304. [PubMed:11794148]
  2. Turpie AG, Bauer KA, Eriksson BI, Lassen MR: Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet. 2002 May 18;359(9319):1721-6. [PubMed:12049860]
  3. Lassen MR, Bauer KA, Eriksson BI, Turpie AG: Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. 2002 May 18;359(9319):1715-20. [PubMed:12049858]
  4. Bauer KA, Eriksson BI, Lassen MR, Turpie AG: Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001 Nov 1;345(18):1305-10. [PubMed:11794149]
  5. Agnelli G, Bergqvist D, Cohen AT, Gallus AS, Gent M: Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg. 2005 Oct;92(10):1212-20. [PubMed:16175516]
  6. Buller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, Prins MH, Raskob G, Segers AE, Cariou R, Leeuwenkamp O, Lensing AW: Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med. 2004 Jun 1;140(11):867-73. [PubMed:15172900]
  7. Buller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, Prins MH, Raskob G, van den Berg-Segers AE, Cariou R, Leeuwenkamp O, Lensing AW: Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med. 2003 Oct 30;349(18):1695-702. [PubMed:14585937]
  8. Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA: Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006 Apr 6;354(14):1464-76. Epub 2006 Mar 14. [PubMed:16537663]
  9. Bassand JP, Richard-Lordereau I, Cadroy Y: Efficacy and safety of fondaparinux in patients with acute coronary syndromes. Expert Rev Cardiovasc Ther. 2007 Nov;5(6):1013-26. [PubMed:18035917]
  10. Steg PG, Jolly SS, Mehta SR, Afzal R, Xavier D, Rupprecht HJ, Lopez-Sendon JL, Budaj A, Diaz R, Avezum A, Widimsky P, Rao SV, Chrolavicius S, Meeks B, Joyner C, Pogue J, Yusuf S: Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial. JAMA. 2010 Sep 22;304(12):1339-49. doi: 10.1001/jama.2010.1320. Epub 2010 Aug 31. [PubMed:20805623]
  11. Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA: Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA. 2006 Apr 5;295(13):1519-30. Epub 2006 Mar 14. [PubMed:16537725]
  12. Kuo KH, Kovacs MJ: Successful treatment of heparin induced thrombocytopenia (HIT) with fondaparinux. Thromb Haemost. 2005 May;93(5):999-1000. [PubMed:15886823]
  13. Ortel TL: Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation. Hematology Am Soc Hematol Educ Program. 2009:225-32. doi: 10.1182/asheducation-2009.1.225. [PubMed:20008202]
  14. Moser M, Bode C: New antithrombotic agents in acute coronary syndromes. Curr Opin Cardiol. 2009 Jul;24(4):313-7. doi: 10.1097/HCO.0b013e32832bd350. [PubMed:19395952]
  15. Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI: Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):141S-159S. doi: 10.1378/chest.08-0689. [PubMed:18574264]
  16. Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW: Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):381S-453S. doi: 10.1378/chest.08-0656. [PubMed:18574271]
  17. Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ: Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):454S-545S. doi: 10.1378/chest.08-0658. [PubMed:18574272]
  18. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE 2nd, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B: ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007 Aug 14;50(7):e1-e157. [PubMed:17692738]
  19. Goodman SG, Menon V, Cannon CP, Steg G, Ohman EM, Harrington RA: Acute ST-segment elevation myocardial infarction: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):708S-775S. doi: 10.1378/chest.08-0665. [PubMed:18574277]
  20. Warkentin TE, Greinacher A, Koster A, Lincoff AM: Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):340S-380S. doi: 10.1378/chest.08-0677. [PubMed:18574270]
  21. Harrington RA, Becker RC, Cannon CP, Gutterman D, Lincoff AM, Popma JJ, Steg G, Guyatt GH, Goodman SG: Antithrombotic therapy for non-ST-segment elevation acute coronary syndromes: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):670S-707S. doi: 10.1378/chest.08-0691. [PubMed:18574276]
  22. Grouzi E, Kyriakou E, Panagou I, Spiliotopoulou I: Fondaparinux for the treatment of acute heparin-induced thrombocytopenia: a single-center experience. Clin Appl Thromb Hemost. 2010 Dec;16(6):663-7. doi: 10.1177/1076029609347900. Epub 2009 Oct 13. [PubMed:19825921]
  23. Blackmer AB, Oertel MD, Valgus JM: Fondaparinux and the management of heparin-induced thrombocytopenia: the journey continues. Ann Pharmacother. 2009 Oct;43(10):1636-46. doi: 10.1345/aph.1M136. Epub 2009 Sep 8. [PubMed:19737996]
  24. Seldrum S, Lambert M, Hainaut P: Heparin-induced thrombocytopenia successfully treated with fondaparinux. Acta Clin Belg. 2009 Mar-Apr;64(2):144-6. doi: 10.1179/acb.2009.024. [PubMed:19432027]
  25. Lobo B, Finch C, Howard A, Minhas S: Fondaparinux for the treatment of patients with acute heparin-induced thrombocytopenia. Thromb Haemost. 2008 Jan;99(1):208-14. doi: 10.1160/TH07-04-0252. [PubMed:18217156]
  26. Ratuapli SK, Bobba B, Zafar H: Heparin-induced thrombocytopenia in a patient treated with fondaparinux. Clin Adv Hematol Oncol. 2010 Jan;8(1):61-5. [PubMed:20351685]
  27. Chong BH, Chong JJ: Heparin-induced thrombocytopenia associated with fondaparinux. Clin Adv Hematol Oncol. 2010 Jan;8(1):63-5. [PubMed:20351686]
External Links
Human Metabolome Database
HMDB0014709
PubChem Compound
49852292
PubChem Substance
46505595
ChemSpider
4445600
ChEBI
61033
ChEMBL
CHEMBL1201202
Therapeutic Targets Database
DNC000658
PharmGKB
PA164746297
HET
NTO
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Fondaparinux_sodium
ATC Codes
B01AX05 — Fondaparinux
AHFS Codes
  • 20:12.04.14 — Direct Factor Xa Inhibitors
PDB Entries
2gd4 / 3evj / 4r9w / 4x7r / 5uf6 / 5wd7
FDA label
Download (289 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionDeep Venous Thrombosis / Pulmonary Embolism (PE)1
1CompletedTreatmentImpaired Renal Function1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Venous Thromboembolism (VTE)1
1CompletedTreatmentCardiac surgery, heparin-induced thrombocytopenia and thrombosis syndrome / Thrombotic events1
1WithdrawnTreatmentObesity, Morbid1
1WithdrawnTreatmentOvarian Carcinoma1
2CompletedPreventionNonvalvular Atrial Fibrillation1
2CompletedPreventionPulmonary Embolism (PE) / Thrombosis, Venous1
2CompletedTreatmentCancer of the Ovary / Cervical Cancers / Endometrial Cancers / Fallopian Tube Cancer / Sarcomas / Thromboembolism / Vaginal Cancers / Vulvar Cancers1
2TerminatedTreatmentCardiac surgery, heparin-induced thrombocytopenia and thrombosis syndrome1
2WithdrawnTreatmentCoronary Heart Disease (CHD) / Myocardial Infarction1
2, 3CompletedPreventionVenous Thromboembolism (VTE)1
2, 3Unknown StatusPreventionDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)1
3CompletedPreventionAbdominal Surgeries / Deep Vein Thrombosis (DVT) / General Surgery / Pulmonary Embolism (PE) / Thromboembolism / Thrombosis, Venous / Venous Thromboembolism (VTE)1
3CompletedPreventionArthroplasty, Replacement, Hip / Thrombosis, Venous / Venous Thromboembolism (VTE)1
3CompletedPreventionGeneral Surgery / Hip Fractures / Thromboembolism1
3CompletedPreventionHip Replacement Surgery / Knee Replacement / Thromboembolism1
3CompletedPreventionThrombosis, Venous1
3CompletedPreventionVenous Thromboembolism (VTE)2
3CompletedTreatmentAcute Deep Vein Thrombosis / Thrombosis, Venous1
3CompletedTreatmentAcute Pulmonary Thromboembolism / Pulmonary Embolism (PE)1
3CompletedTreatmentMyocardial Infarction / Thromboembolism1
3CompletedTreatmentSuperficial Vein Thrombosis1
3CompletedTreatmentThrombosis, Venous1
3RecruitingTreatmentDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
3TerminatedPreventionThrombosis, Venous1
3TerminatedPreventionVenous Thromboembolism (VTE)1
3TerminatedTreatmentMalignancies / Thromboembolism1
3Unknown StatusTreatmentCoronary Bypass Graft Failure/Occlusion1
4Active Not RecruitingPreventionMedical Patients / Thrombocytopenias1
4CompletedPreventionMajor Orthopaedic Surgery and Renal Impairment1
4CompletedPreventionVenous Thromboembolism (VTE)1
4CompletedTreatmentPrimary Total Hip and Knee Arthroplasty1
4TerminatedPreventionImpaired Renal Function / Medical Patients1
4Unknown StatusTreatmentKnee Replacement Surgery1
4WithdrawnTreatmentPulmonary Embolism (PE)1
4WithdrawnTreatmentCardiac surgery, heparin-induced thrombocytopenia and thrombosis syndrome1
Not AvailableCompletedNot AvailableAcute Coronary Syndromes (ACS)1
Not AvailableCompletedNot AvailableAcute HIT II (Heparin-induced Thrombocytopenia Type II)1
Not AvailableCompletedNot AvailableAtaxia2
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD)2
Not AvailableCompletedNot AvailableThromboembolism / Venous Thromboembolism (VTE)1
Not AvailableCompletedNot AvailableThrombosis, Venous3
Not AvailableCompletedNot AvailableUnsuspected Pulmonary Embolism1
Not AvailableCompletedPreventionNeoplasms, Esophageal / Neoplasms, Lung / Venous Thromboembolism (VTE)1
Not AvailableCompletedTreatmentDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)1
Not AvailableRecruitingTreatmentBlood Clots / Deep Vein Thrombosis (DVT) / Malignancies / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
Not AvailableTerminatedPreventionThrombosis, Venous1
Not AvailableTerminatedTreatmentPatients With Acute Renal Failure / Renal Failure1
Not AvailableUnknown StatusTreatmentCoronary Artery Bypass Graft Surgery Patients / Deep Vein Thrombosis (DVT) / Venous Thromboembolism (VTE)1
Not AvailableUnknown StatusTreatmentPulmonary Embolism (PE)1
Not AvailableWithdrawnNot AvailablePulmonary Embolism (PE)1
Not AvailableWithdrawnBasic ScienceKidney Diseases1

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
Packagers
  • GlaxoSmithKline Inc.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
Injection, solutionIntravenous; Subcutaneous2.5 mg/0.5ml
Injection, solutionSubcutaneous1.5 mg/0.3ml
Injection, solutionSubcutaneous10 mg/0.8ml
Injection, solutionSubcutaneous2.5 mg/0.5mL
Injection, solutionSubcutaneous5 mg/0.4ml
Injection, solutionSubcutaneous7.5 mg/0.6ml
InjectionSubcutaneous10 mg/0.8mL
InjectionSubcutaneous2.5 mg/0.5mL
InjectionSubcutaneous5 mg/0.4mL
InjectionSubcutaneous7.5 mg/0.6mL
SolutionIntravenous; Subcutaneous2.5 mg
SolutionSubcutaneous10 mg
SolutionSubcutaneous5 mg
SolutionSubcutaneous7.5 mg
Prices
Unit descriptionCostUnit
Arixtra 7.5 mg/0.6ml Solution 0.6ml Syringe148.62USD syringe
Arixtra 2.5 mg/0.5ml Solution 0.5ml Syringe63.15USD syringe
Arixtra (0.5 Ml Syringe) 2.5 mg/syr Syringe17.38USD syringe
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP0.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.91 mg/mLALOGPS
logP-1.6ALOGPS
logP-10ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)-3ChemAxon
Physiological Charge-10ChemAxon
Hydrogen Acceptor Count44ChemAxon
Hydrogen Donor Count19ChemAxon
Polar Surface Area805.48 Å2ChemAxon
Rotatable Bond Count27ChemAxon
Refractivity255.85 m3·mol-1ChemAxon
Polarizability122.56 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9857
Blood Brain Barrier-0.8953
Caco-2 permeable-0.6312
P-glycoprotein substrateNon-substrate0.6876
P-glycoprotein inhibitor INon-inhibitor0.6169
P-glycoprotein inhibitor IINon-inhibitor0.9493
Renal organic cation transporterNon-inhibitor0.9327
CYP450 2C9 substrateNon-substrate0.8037
CYP450 2D6 substrateNon-substrate0.8179
CYP450 3A4 substrateNon-substrate0.5537
CYP450 1A2 substrateNon-inhibitor0.7505
CYP450 2C9 inhibitorNon-inhibitor0.7664
CYP450 2D6 inhibitorNon-inhibitor0.8799
CYP450 2C19 inhibitorNon-inhibitor0.757
CYP450 3A4 inhibitorNon-inhibitor0.9208
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9172
Ames testNon AMES toxic0.5944
CarcinogenicityNon-carcinogens0.763
BiodegradationNot ready biodegradable0.8922
Rat acute toxicity2.4465 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8431
hERG inhibition (predictor II)Non-inhibitor0.6468
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory a...
Gene Name
SERPINC1
Uniprot ID
P01008
Uniprot Name
Antithrombin-III
Molecular Weight
52601.935 Da
References
  1. Paolucci F, Clavies MC, Donat F, Necciari J: Fondaparinux sodium mechanism of action: identification of specific binding to purified and human plasma-derived proteins. Clin Pharmacokinet. 2002;41 Suppl 2:11-8. [PubMed:12383040]
  2. Cheng JW: Fondaparinux: a new antithrombotic agent. Clin Ther. 2002 Nov;24(11):1757-69; discussion 1719. [PubMed:12501872]
  3. Dager WE, Andersen J, Nutescu E: Special considerations with fondaparinux therapy: heparin-induced thrombocytopenia and wound healing. Pharmacotherapy. 2004 Jul;24(7 Pt 2):88S-94S. [PubMed:15317404]
  4. Donat F, Duret JP, Santoni A, Cariou R, Necciari J, Magnani H, de Greef R: The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet. 2002;41 Suppl 2:1-9. [PubMed:12383039]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type endopeptidase activity
Specific Function
Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
Gene Name
F10
Uniprot ID
P00742
Uniprot Name
Coagulation factor X
Molecular Weight
54731.255 Da
References
  1. Grouzi E, Kyriakou E, Panagou I, Spiliotopoulou I: Fondaparinux for the treatment of acute heparin-induced thrombocytopenia: a single-center experience. Clin Appl Thromb Hemost. 2010 Dec;16(6):663-7. doi: 10.1177/1076029609347900. Epub 2009 Oct 13. [PubMed:19825921]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 04:43