Fondaparinux Brand Name– Arixtra
What is Fondaparinux
- Fondaparinux is a synthetic pentasaccharide anticoagulant used for the treatment of deep vein thrombosis (DVT) or pulmonary embolism (PE) and for the prevention of DVT and PE in patients undergoing abdominal surgery, hip fracture surgery, hip replacement, or knee replacement surgery.
- Fondaparinux is the first in a new class of agents, an indirect factor Xa inhibitor, which selectively inhibits factor Xa via antithrombin-dependent actions.
- Unlike unfractionated heparin or low molecular weight heparins (LMWHs), fondaparinux does not inhibit thrombin (factor IIa).
- Therefore, fondaparinux inhibits a single, targeted step in the coagulation cascade (factor Xa), resulting in antithrombotic action. In contrast to heparin anticoagulants, fondaparinux does not require laboratory monitoring and lacks a specific antidote in the event of excessive anticoagulation.
- The FDA approved fondaparinux (Arixtra®) in December 2001. It was also approved by the FDA for extended prophylaxis of DVT in patients undergoing hip surgery in June 2003, for the treatment of DVT or PE when administered in conjunction with warfarin in May 2004, and for DVT and PE prophylaxis in at-risk patients undergoing abdominal surgery in May 2005.
What are the Indications
- acute myocardial infarction
- coronary artery thrombosis prophylaxis
- deep venous thrombosis (DVT)
- deep venous thrombosis (DVT) prophylaxis
- pulmonary embolism
- pulmonary embolism prophylaxis
- superficial vein thrombosis
- unstable angina
For the treatment of acute pulmonary embolism (PE) or acute deep venous thrombosis (DVT) in conjunction with warfarin
What are the Side Effects
- anaphylactoid reactions
- anemia
- angioedema
- bleeding
- confusion
- dizziness
- ecchymosis
- elevated hepatic enzymes
- epistaxis
- GI bleeding
- headache
- hematemesis
- hematoma
- hematuria
- hypokalemia
- hypotension
- infection
- injection site reaction
- insomnia
- intracranial bleeding
- melena
- ocular hemorrhage
- petechiae
- pruritus
- purpura
- rash
- retroperitoneal bleeding
- spinal hematoma
- thrombocytopenia
Monitoring Parameters
- anti-Xa activity
- hemoglobin/hematocrit
- platelet count
- prothrombin time (PT)
- serum creatinine/BUN
- stool guaiac
Mechanism of Action
- Fondaparinux exerts antithrombotic activity as a result of antithrombin III (ATIII)-mediated selective inhibition of factor Xa. Fondaparinux is a copy of the antithrombin III binding area of heparin.
- When fondaparinux binds to ATIII, a permanent conformation change in the ATIII molecule allows an increased affinity for factor Xa. The increased affinity potentiates ATIII’s ability to inhibit factor Xa by roughly 300-fold.
- Neutralization of factor Xa interrupts the blood coagulation cascade that leads to thrombin formation and thrombus development.
- A single fondaparinux molecule is recycled and re-binds to several consecutive ATIII molecules. The structurally changed ATIII-Xa complex is then cleared from circulation.
- The anti-Xa activity of fondaparinux reaches a maximum value in roughly 3 hours. Fondaparinux does not inactivate thrombin (factor IIa) and has no known effect on platelet function.
- At recommended doses, fibrinolytic activity or bleeding time is not altered. An antidote to reverse bleeding effects of fondaparinux is not available; however, one is under investigation.
What are the contraindications
Here are the Contraindications of Fondaparinux
- aneurysm
- anticoagulant therapy
- bleeding
- breast-feeding
- children
- dental disease
- dental work
- diabetic retinopathy
- diverticulitis
- endocarditis
- epidural anesthesia
- geriatric
- GI bleeding
- hemophilia
- heparin-induced thrombocytopenia (HIT)
- hepatic disease
- history of angioedema
- hypertension
- immune thrombocytopenic purpura (ITP)
- infants
- inflammatory bowel disease
- intramuscular administration
- intramuscular injections
- labor
- lumbar puncture
- menstruation
- neonates
- obstetric delivery
- peptic ulcer disease
- pregnancy
- renal disease
- renal failure
- renal impairment
- spinal anesthesia
- stroke
- surgery
- thrombocytopenia
- thrombolytic therapy
- vaginal bleeding
What are the drug to drug Interactions
- Abciximab
- Acetaminophen; Aspirin, ASA; Caffeine
- Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
- Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
- Ado-Trastuzumab emtansine
- Alteplase
- Altretamine
- Aminosalicylate sodium, Aminosalicylic acid
- Amlodipine; Celecoxib
- Anagrelide
- Antithrombin III
- Antithymocyte Globulin
- Apixaban
- Argatroban
- Arsenic Trioxide
- Aspirin, ASA
- Aspirin, ASA; Butalbital; Caffeine
- Aspirin, ASA; Butalbital; Caffeine; Codeine
- Aspirin, ASA; Caffeine; Dihydrocodeine
- Aspirin, ASA; Caffeine; Orphenadrine
- Aspirin, ASA; Carisoprodol
- Aspirin, ASA; Carisoprodol; Codeine
- Aspirin, ASA; Citric Acid; Sodium Bicarbonate
- Aspirin, ASA; Dipyridamole
- Aspirin, ASA; Omeprazole
- Aspirin, ASA; Oxycodone
- Aspirin, ASA; Pravastatin
- Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
- Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
- Betrixaban
- Bismuth Subsalicylate
- Bismuth Subsalicylate; Metronidazole; Tetracycline
- Bivalirudin
- Caplacizumab
- Carbenicillin
- Celecoxib
- Chlorambucil
- Choline Salicylate; Magnesium Salicylate
- Cilostazol
- Clofarabine
- Clopidogrel
- Collagenase
- Cytarabine, ARA-C
- Dabigatran
- Dalteparin
- Danaparoid
- Danazol
- Dasatinib
- Decitabine
- Deferasirox
- Defibrotide
- Denileukin Diftitox
- Desirudin
- Dextran
- Diclofenac
- Diclofenac; Misoprostol
- Diflunisal
- Diphenhydramine; Ibuprofen
- Diphenhydramine; Naproxen
- Dipyridamole
- Drotrecogin Alfa
- Edoxaban
- Eltrombopag
- Enoxaparin
- Epoprostenol
- Eptifibatide
- Esomeprazole; Naproxen
- Esterified Estrogens; Methyltestosterone
- Estramustine
- Etodolac
- Factor X
- Famotidine; Ibuprofen
- Fenoprofen
- Fish Oil, Omega-3 Fatty Acids (Dietary Supplements)
- Floxuridine
- Fluorouracil, 5-FU
- Flurbiprofen
- Folate analogs
- Garlic, Allium sativum
- Ginger, Zingiber officinale
- Ginkgo, Ginkgo biloba
- Green Tea
- Hemin
- Heparin
- Hydrocodone; Ibuprofen
- Hydroxyurea
- Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
- Ibritumomab Tiuxetan
- Ibrutinib
- Ibuprofen
- Ibuprofen; Oxycodone
- Ibuprofen; Pseudoephedrine
- Icosapent ethyl
- Iloprost
- Imatinib
- Indomethacin
- Inotersen
- Interferon Alfa-2a
- Interferon Alfa-2b
- Interferon Alfa-2b; Ribavirin
- Interferon Alfa-n3
- Interferon Alfacon-1
- Intravenous Lipid Emulsions
- Ketoprofen
- Ketorolac
- Lansoprazole; Naproxen
- Lepirudin
- Lomustine, CCNU
- Magnesium Salicylate
- Meclofenamate Sodium
- Mefenamic Acid
- Meloxicam
- Methoxsalen
- Methylsulfonylmethane, MSM
- Methyltestosterone
- Mifepristone
- Miltefosine
- Mycophenolate
- Nabumetone
- Nandrolone Decanoate
- Naproxen
- Naproxen; Pseudoephedrine
- Naproxen; Sumatriptan
- Natural Antineoplastics
- Nelarabine
- Nintedanib
- Nonsteroidal antiinflammatory drugs
- Obinutuzumab
- Omacetaxine
- Orlistat
- Oxandrolone
- Oxaprozin
- Pentosan
- Phentermine; Topiramate
- Piperacillin
- Piperacillin; Tazobactam
- Piroxicam
- Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
- Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
- Prasugrel
- Prothrombin Complex Concentrate, Human
- Reteplase, r-PA
- Rivaroxaban
- Rofecoxib
- Salicylates
- Salsalate
- Selective serotonin reuptake inhibitors
- Serotonin norepinephrine reuptake inhibitors
- Sodium Hyaluronate, Hyaluronic Acid
- Sodium Iodide
- Streptokinase
- Sulfinpyrazone
- Sulindac
- Telavancin
- Tenecteplase
- Thrombin Inhibitors
- Thrombolytic Agents
- Ticagrelor
- Ticarcillin
- Ticarcillin; Clavulanic Acid
- Ticlopidine
- Tinzaparin
- Tipranavir
- Tirofiban
- Tolmetin
- Topiramate
- Trazodone
- Treprostinil
- Tretinoin, ATRA
- Urokinase
- Valdecoxib
- Verteporfin
- Vilazodone
- Vorapaxar
- Vorinostat
- Vortioxetine
- Warfarin
What does current research says?
- Current evidence suggest that fondaparinux is as effective as, if not more than, enoxaparin in the prevention of venous thromboembolism in the postoperative period.
- It has also been found to have similar effectiveness to enoxaparin and unfractionated heparin in the treatment of venous and pulmonary embolism, respectively.
- In the field of cardiology, studies have demonstrated that in the setting of acute coronary syndromes, treatment with fondaparinux is not inferior to enoxaparin in preventing major cardiac outcomes, but it is associated with lower risk of bleeding complications, irrespective of the use of percutaneous coronary intervention.
- During percutaneous coronary intervention, there is a slightly increased risk of catheter thrombosis, which is removed when used along with unfractionated heparin.
- However, in patients with ST-elevation myocardial infarction, the benefit has been shown in those either receiving thrombolysis or not undergoing any revascularization, but not in subjects undergoing primary percutaneous coronary intervention where unfractionated heparin is still preferred.
