|Synonyms:||Apixaban;Apixaban, BMS 562247-01;1H-Pyrazolo[3,4-c]pyridine-3-carboxamide, 4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-;1-(4-Methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide;BMS 562247-01;1-(4-Methoxy-phenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid aMide;1-(4-Methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,
5-dihydropyrazolo[3,4-c]pyridine-3-carboxaMide;Nilotinib and its interMediate|
|Apixaban Chemical Properties|
|Apixaban Usage And Synthesis|
|Novel oral Factor Xa inhibitor||Apixaban is a novel kind of oral factor Xa factor inhibitor jointly developed by Bristol-Myers Squibb Company and Pfizer Company with the trade name being Eliquis. It is a novel oral anticoagulant. Through inhibiting an important blood coagulation factor Xa, apixaban can be used for preventing thrombin formation and thrombus formation. |
On April 26, 2007, Bristol-Myers Squibb, together with Pfizer and announced that they will cooperate for development of the Bristol-Myers Squibb-owned novel oral anticoagulant apixaban to be the upgrade alternative of warfarin. According to the cooperation agreement, Pfizer will pre-pay $250 million to Bristol-Myers Squibb for undertaking 60% of the total developmental costs of anticoagulant apixaban (started from January 1, 2007), and Bristol Bristol-Myers Squibb will undertake the remaining 40 percent to obtain co-development and marketing rights of this drug.
In May 2011, apixaban has been first approved at 27 EU countries and Iceland, Norway for the prevention of the venous thromboembolism in the elective replacement surgery of hip or knee.
On November 20, 2012, the European Commission had approved Eliquis (apixaban) for the prevention of embolism of apoplexy and systemic circulation of patients of non-valvular atrial fibrillation (NVAF) with one or more risk factors. Subsequently, Canada Food and Drug Administration, Japan and the US FDA had approved Eliquis (Apixaban) for the prevention of embolism of apoplexy and systemic circulation of patients of non-valvular atrial fibrillation (NVAF) with one or more risk factors.
On April 12, 2013, the novel anticoagulant, Eliquis, jointly developed by the Bristol-Myers Squibb and Pfizer has been officially marketed in China. Eliquis is a novel orally administrated Xa factor inhibitor for being applied to the adult patients who have been subject to elective hip or knee replacement surgery in adult patients for the prevention of venous thromboembolism (VTE). Its marketing has provided novel safe and effective choice for the anticoagulation of clinical orthopedic surgery, bringing new hope to the Chinese patients subjecting to hip/knee elective replacement surgery in patients. Clinical studies have demonstrated that, compared with the efficacy of subcutaneous injection of enoxaparin 40 mg once per day, oral administration of 2.5 mg of Eliquis (apixaban) twice daily can give a better efficacy in prevention of the venous thromboembolic events in the hip or knee replacement surgery better without increasing the risk of bleeding.
|Pharmacological effects||Apixaban is a selective inhibitor of activated factor X for oral administration and can prevent blood clots with the side effects of bleeding being lower than the old drug warfarin for being used for the prevention of thrombus for patients who have been subject to hip or knee replacement surgery.
|Clinical evaluation||Apixaban is the third novel oral marketed anticoagulant following dabigatran and rivaroxaban. It has been approved in Europe for the prevention of venous thromboembolism (VTE) in patients who have been subject to elective hip or knee replacement surgery. |
For the three oral anticoagulants approved by European, compared with the current standard treatment for post-orthopedic surgery prevention of venous thromboembolism through enoxaparin, rivaroxaban and apixaban have exhibited their advantages in the RECORD trials and ADVANCE trials. Experts said that, put these results side by side, it seems that the efficacy of rivaroxaban was slightly better but with a more severe bleeding condition than apixaban. Experts attributed these differences to the time of administration, in the RECORD trial the rivaroxaban was administered at 6-8 hours after surgery while in the ADVANCE trial apixaban is administered at 18 hours after surgery. The closer the drug administration time to the surgery, the better its efficacy will be, but the higher the risk of bleeding.
Myers Squibb Bristol/ Pfizer advertised using the medication time of apixaban in ADVANCE trial, said apixaban is the only orally administrated anticoagulant drug with the medication window period time being 12-24 hours in the first time of administration after surgery, being able to help physician to observe fist before starting treatment after operation and stabilize the condition. However, novel oral anticoagulant rivaroxaban (once daily), also has its own advantages.
Another kind of anticoagulant drug, dabigatran, hasn’t shown comparable anticoagulant effect in orthopedics as the above two drugs. It is only shown to be not inferior to the current standard treatment effect in only two studies while still being inferior in other trials. But Dabigatran is the first novel anticoagulant drug approved by the US FDA (in October 2010) which can be used for treating non-valvular atrial fibrillation and has already been approved in the United States and Canada for the prevention of stroke in patients with atrial fibrillation. Though, rivaroxaban has also exhibited good results for this indication, it has been not yet approved.
The above information is edited by the Chemicalbook of Dai Xiongfeng. Source: tjipr.
|Patent cases||Compound international patent: WO2003026652; publication date: 2003-04-03. |
Compound patent in China: CN1578660, announcement date: 2005-02-09, patent expiration time: 2025-02-09, it can’t be developed due to the patent issue.
|Drug Interactions||1. Strong CYP3A4 and P-gp dual inhibitors can increase the apixaban blood levels: reduce the dose of LIQUIS to 2.5 mg or avoid using simultaneously. |
2. Simultaneous administration of strong CYP3A4 and P-gp inducers can reduce the apixaban blood levels: avoid simultaneous administration.
|Use in specific populattons||1. Lactating Mothers: discontinue lactating or discontinue the drug. |
2. Pregnancy: not recommended.
3. Patients of severe hepatic impairment: not recommended.
|Usage||Apixaban is a highly selective, reversible inhibitor of Factor Xa with Ki of 0.08 nM and 0.17 nM in human and rabbit, respectively.|
|Apixaban Preparation Products And Raw materials|