Fondaparinux (trade name Arixtra) is an anticoagulant medication chemically related to low molecular weight heparins. It is marketed by GlaxoSmithKline. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratories.
STRUCTURE AND MECHANISM
Fondaparinux is a synthetic pentasaccharide Factor Xa inhibitor. 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 glycosaminoglycans heparin and heparan sulfate (HS). Within heparin and heparan sulfate this monomeric sequence is thought to form the high affinity binding site for the 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. In contrast to heparin, fondaparinux does not inhibit thrombin.
Administration
Fondaparinux is given subcutaneously daily. Clinically, it is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism.
Comparison to other agents
One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for heparin-induced thrombocytopenia (HIT) is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anticoagulate patients with established HIT as it has no affinity to PF-4. However, its renal excretion precludes its use in patients with renal dysfunction.
Unlike direct factor Xa inhibitors, it mediates its effects indirectly through antithrombin III, but unlike heparin, it is selective for factor Xa.
Uses
Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity.
It has been investigated for use in conjunction with streptokinase.
fondaparinux vs control | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NCT00320398(ongoing) NCT00320398 | Fondaparinux versus | patients undergoing either an elective primary total hip replacement (THR) surgery or a revision of a THR | Follow-up: double-blind Japan | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NCT00333021(ongoing) NCT00333021 | Fondaparinux versus | Abdominal Surgery | Follow-up: open japan | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
fondaparinux vs no treatment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PROTECT (fundaparinux)(ongoing) NCT00881088 | fondaparinux 2,5 mg daily group during immobilization versus no treatment | Patients with a nonsurgical fracture of the lower extremity immobilised in a below-knee plaster cast | Follow-up: single blind | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
fondaparinux vs placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
DRI4757(unpublished) | fondaparinux subcutaneously at 0.75, 1.5, 2.5, and 3.0 mg for at least 10 calendar days, (with a maximum of 14 days) versus placebo | Japanese patients undergoing elective total knee replacement surgery | Follow-up: 14 days double blind Japan | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ARTEMIS (Cohen) ,2006 | Fondaparinux 2.5 mg once daily for 6–14 days versus placebo | High-risk medical patients | Follow-up: 6-15 days double blind 8 countries | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
fondaparinux vs placebo (on top intermittent pneumatic comp.) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
APOLLO (Turpie) ,2007 | fondaparinux 2.5 mg s.c. for 5-9 days, starting 6-8 h postoperatively + intermittent pneumatic compression versus placebo s.c. for 5-9 days, starting 6-8 h postoperatively + intermittent pneumatic compression | Patients aged at least 40 years undergoing abdominal surgery | Follow-up: 10 days double blind US | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
fondaparinux vs control | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sasaki ,2010 | fondaparinux 2.5mg daily for 14 days versus usual care | patients undergoing hip fracture surgery | Follow-up: 14 days open Japan | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
fondaparinux vs enoxaparin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PENTAMAKS (Bauer) ,2001 | fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery versus enoxaparin 30mg twice daily (North america recommendation) | elective major knee surgery | Follow-up: 11 days double blind North america | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PENTHIFRA (Eriksson) ,2001 | fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery versus enoxaprin 40mg once daily | hip fracture surgery | Follow-up: 11 days double blind 21 countries | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PENTATHLON (Turpie) ,2002 | fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery versus enoxaparin 30mg twice daily (North america recommendation) | elective hip replacement surgery | Follow-up: 11 days double blind USA, Canada, Australia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
EPHESUS (Lassen) ,2002 | fondaparinux 2.5-mg once-daily subcutaneous, starting 6 hours after surgery versus enoxaprin 40mg once daily | elective hip replacement surgery | Follow-up: 11 days (6 weeks) double blind 16 European countries | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Turpie ,2001 | pentasaccharide Org31540/SR90107A subcutaneous once daily at doses 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0 mg versus enoxaparin 30mg once daily subcutaneous | patients undergoing total hip replacement | Follow-up: >15 days double blind US, Canada, Autralia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
L8541(unpublished) | fondaparinux 2.5mg subcutaneous once-daily for 7+/-2 days versus enoxaparin 40mg s.c. once-daily | chinese patients undergoing major orthopaedic surgery of the lower limbs | Follow-up: 9 days (49d) single-blind China | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
L8635(unpublished) | Fondaparinux 2.5mg once daily subcutaneously for 7 days versus enoxaparin 40mg once daily SC for 7 days | Taiwanese patients undergoing elective knee replacement | Follow-up: 10 days open, blind assessment Taiwan | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
BRiEF NCT00521885 | fondaparinux 2.5mg qd versus enoxaparin 40mg qd | acute medically ill, non-surgical patients | Follow-up: Germany | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PEGASUS ,2005 | once-daily subcutaneous injections of fondaparinux 2·5 mg started 6 h after surgery for 5–9 days versus once-daily subcutaneous injections of dalteparin 5000 units for 5–9 days (2500 units each, given 2 h before surgery and 12 h after the preoperative administration) | patients undergoing major abdominal surgery | Follow-up: 10 days (30 days) double blind 22 countries | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
fondaparinux vs nadroparin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
FONDACAST(ongoing) NCT00843492 | subcutaneously, once daily, fondaparinux 2.5 mg for at least 21 Days, up to complete mobilization, with a maximal duration of treatment of 45 days versus daily nadroparin 2850 anti-Xa IU (0.3 mL) for at least 21 Days, up to complete mobilization | patients requiring rigid or semi-rigid immobilization for at least 21 days and up to 45 days because of isolated non-surgical below-knee injury | Follow-up: 5 weeks open Europe | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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