- Available:In stock1345
- Availability date:2020-07-30
- Dosage form:Tablets
- In stock:1345 Items
active ingredient: apixaban;
1 film-coated tablet contains 2.5 mg of apixaban;
excipients: lactose anhydrous, microcrystalline cellulose, sodium croscarmellose, sodium lauryl sulfate, magnesium stearate, Opadry® II Yellow (hypromellose 15 CP; lactose, monohydrate; titanium dioxide (e 171); triacetin; iron oxide yellow (E 172)).
Basic physical and chemical properties: yellow, round, biconvex film-coated tablets with the inscription "893" on one side and "2 1/2" on the other.
Antithrombotic drugs. Direct factor Xa inhibitors. ATX code B01 AF02.
Mechanism of action.
Apixaban is a potent reversible direct and highly selective inhibitor of the active site of Factor Xa, intended for oral administration. For antithrombotic action, it does not need antithrombin III. Apixaban inhibits free and blood clot-bound Factor Xa, as well as inhibits prothrombinase activity. Apixaban does not directly affect platelet aggregation, but indirectly inhibits the thrombin-induced platelet aggregation process. By inhibiting Factor Xa, apixaban prevents the formation of thrombin and the formation of a blood clot. Preclinical studies of apixaban in animals have shown the effectiveness of the antithrombotic effect of the drug for the Prevention of arterial and venous thrombosis when taken in doses that do not disrupt the processes of hemostasis.
The pharmacodynamics of apixaban reflects its mechanism of action (inhibition of Factor Xa). As a result of Factor Xa inhibition, apixaban increases the values of such indicators as prothrombin time (if), international normalized ratio (MHC) and activated partial thromboplastin time (aptt). The changes observed in blood clotting parameters when used at therapeutic doses are insignificant and extremely variable, and they are not recommended for evaluating the pharmacodynamic properties of apixaban. During the analysis of thrombin formation, apixaban reduced the endogenous potential of thrombin — a quantitative indicator of thrombin formation in human blood plasma.
Apixaban also shows activity against Factor Xa inhibition, which is confirmed by a decrease in the enzymatic activity of Factor Xa from the results of evaluation using different commercial kits to detect Factor Xa inhibition, although the specific results for different kits differed. The results of clinical trials are available only for chromogenic analysis of Rotachrom® heparin. Factor Xa inhibition activity is associated with plasma apixaban concentrations. This relationship is close to linear, and the maximum activity of Factor Xa inhibition is observed when peak plasma concentrations of apixaban are reached. The relationship between the concentration of apixaban in blood plasma and the activity of Factor Xa inhibition is approximately linear over a wide range of apixaban doses.
Prevention of venous thromboembolism in adult patients who have undergone elective knee or hip replacement surgery.
Prevention of strokes and systemic embolism in adult patients with non-Valve atrial fibrillation who have one or more risk factors, such as a history of stroke or transient ischemic attack, age 75 years or more, hypertension, diabetes mellitus, symptomatic heart failure (at least Class II according to the New York Heart Association classification).
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as prevention of relapses of DVT and PE in adults (for information on patients with PE and unstable hemodynamics, see the section "application features").
Hypersensitivity to the active substance or to any auxiliary component.
Clinically significant active bleeding.
Liver diseases that are accompanied by coagulopathy and a clinically significant risk of bleeding.
Pathology or condition accompanied by a significant risk of heavy bleeding (e.g. existing or recently suffered gastrointestinal peptic ulcer, presence of malignancies with a high risk of bleeding, fresh brain or spinal cord injuries, recent brain, spinal cord or ophthalmic interventions, recent intracranial bleeding, diagnosed or suspected esophageal varicose veins, arteriovenous malformations, vascular aneurysms, pronounced intra-vertebral or intracranial vascular abnormalities).
Concomitant use of any other anticoagulants, such as unfractionated heparin, low-molecular-weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (Fondaparinux, etc.), oral anticoagulants (warfarin, rivaroxaban, dabigatran, etc.), except in specific cases of changes in anticoagulant therapy (see below). administration of unfractionated heparin in doses necessary to ensure patency of the central venous or arterial catheter, or administration of unfractionated heparin during catheter ablation for the treatment of atrial fibrillation (see the sections "application features" and "interactions with other drugs and other types of interactions").
Interactions with other drugs and other types of interactions
CYP3A4 and P-gp inhibitors.
Concomitant administration of apixaban and ketoconazole (400 mg 1 time daily), which is a potent inhibitor of CYP3A4 and P-gp, resulted in a 2-fold increase in Mean AUC and a 1.6-fold increase in Mean CMax of apixaban.
ELIQUIS is not recommended for patients receiving systemic treatment with powerful CYP3A4 and P-gp inhibitors, such as azole antimycotics (e.g. ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (e.g. ritonavir) (see Section "special instructions for use").
Active substances that are not considered potent inhibitors of CYP3A4 and P-gp (for example, amiodarone, clarithromycin, diltiazem, fluconazole, naproxen, quinidine, verapamil) are expected to increase apixaban concentrations less intensively in plasma. There is no need to adjust the dose of apixaban when it is co-administered with substances that are not strong inhibitors of CYP3A4 and/or P-gp. For example, diltiazem (at a dosage of 360 mg 1 time per day), which is considered a moderate CYP3A4 inhibitor and a weak P-gp inhibitor, resulted in a 1.4-fold increase in the average AUC and a 1.3-fold increase in the average Cmax of apixaban. Naproxen (a single dose of 500 mg) is a P-gp inhibitor, but does not affect CYP3A4. This drug resulted in a 1.5-fold increase in Mean AUC and a 1.6-fold increase in Mean CMax of apixaban. Clarithromycin (500 mg, twice daily), A P-gp inhibitor, and a strong CYP3A4 inhibitor resulted in a 1.6-fold and 1.3-fold increase in the mean AUC and Cmax of apixaban, respectively.
Inducers of CYP3A4 and P-gp.
Concomitant administration of apixaban and rifampicin (a potent inducer of CYP3A4 and P-gp) resulted in a decrease in the mean AUC and Cmax of apixaban by approximately 54% and 42%, respectively. Concomitant use of apixaban and other powerful inducers of CYP3A4 and P-gp (for example, phenytoin, carbamazepine, phenobarbital, or St. John's wort) may also lead to a decrease in the concentration of apixaban in blood plasma. Dose adjustment of apixaban is not necessary if it is used simultaneously with similar drugs. However, apixaban should be used with caution to prevent VTE during elective hip or knee replacement surgery, prevent stroke and systemic embolism in patients with non-valvular atrial fibrillation (NFP), and prevent relapses of DVT and PE.
Apixaban is not recommended for the treatment of DVT and PE in patients who are simultaneously receiving systemic treatment with powerful inducers of CYP3A4 and P-gp, since its effectiveness may be impaired (see the section "application specifics").
Anticoagulants, platelet aggregation inhibitors, selective serotonin reuptake inhibitors (SSRIs) or serotonin/norepinephrine reuptake inhibitors (SSRIs), and nonsteroidal anti-inflammatory drugs (NSAIDs).
Due to the increased risk of bleeding, concomitant use of any other anticoagulants in patients is contraindicated, except in specific circumstances of changing anticoagulant therapy, when unfractionated heparin is administered at doses necessary to ensure patency of the central venous or arterial catheter, or unfractionated heparin is administered during catheter ablation for the treatment of atrial fibrillation (see Section "contraindications").
After combined administration of enoxaparin (a single dose of 40 mg) and apixaban (a single dose of 5 mg), an additive effect on the activity of the Anti-Xa factor was observed.
When apixaban and acetylsalicylic acid were co-administered (325 mg once a day), there were no pronounced pharmacokinetic or pharmacodynamic interactions.
Concomitant use of apixaban with clopidogrel (75 mg 1 time per day) or with a combination of 75 mg of clopidogrel and 162 mg of acetylsalicylic acid 1 time per day, or with Prasugrel (initial dose – 60 mg, subsequent dosage – 10 mg 1 time per day) in Phase I studies did not reveal a significant increase in Model bleeding time or additional inhibition of platelet aggregation compared to the use of antiplatelet drugs without apixaban. An increase in blood clotting parameters (if, MHC, and aptt) was consistent with the effects of apixaban as monotherapy.
Naproxen (500 mg), which is a P-gp inhibitor, resulted in a 1.5-fold increase in Mean AUC and a 1.6-fold increase in Mean CMax of apixaban. Apixaban caused a corresponding increase in blood clotting parameters. Concomitant use of naproxen and apixaban did not change the effect of naproxen on platelet aggregation due to the influence of arachidonic acid, and did not lead to a clinically significant increase in bleeding time. Despite this, individuals may develop a more pronounced pharmacodynamic response to concomitant administration of antiplatelet drugs and apixaban. ELIQUIS should be used with caution in combination with SSRIs/IZZS, NSAIDs, acetylsalicylic acid and/or P2Y12 inhibitors, as these drugs usually increase the risk of bleeding (see the section "special instructions for use").
There is limited experience of concomitant use with other platelet aggregation inhibitors (such as GPIIb/IIIA receptor antagonists, Dipyridamole, dextran, or sulfinpyrazone) or thrombolytic agents. Since such drugs increase the risk of bleeding, their simultaneous use together with ELIQUIS is not recommended (see the section "features of use").
Other concomitant medications.
No clinically pronounced pharmacokinetic or pharmacodynamic interactions were observed with concomitant use of apixaban and atenolol or Famotidine. Concomitant administration of 10 mg of apixaban and 100 mg of atenolol did not have a clinically significant effect on the pharmacokinetics of apixaban. After further Administration of two drugs simultaneously, the average AUC and Cmax values of apixaban were lower by 15% and 18%, respectively, compared to use as monotherapy. Concomitant administration of 10 mg of apixaban and 40 mg of Famotidine did not affect the AUC or Cmax of apixaban.
Effect of apixaban on other medications.
In vitro studies of apixaban showed no inhibitory effect of this drug on the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (IC50 > 45 mmol/L) and the presence of a weak inhibitory effect on the activity of CYP2C19 (IC50 > 20 mmol/L) at concentrations significantly higher than the peak plasma concentrations of the drug in patients. Apixaban at concentrations up to 20 mmol/L does not induce the activity of CYP1A2, CYP2B6, or CYP3A4/5. Therefore, it is believed that apixaban will not change the metabolic clearance of concomitant drugs, the metabolism of which occurs with the participation of these enzymes. Apixaban does not significantly inhibit P-gp activity.
As described below, in studies involving healthy volunteers, apixaban did not lead to significant changes in the pharmacokinetics of digoxin, naproxen, or atenolol.
Digoxin. Concomitant administration of apixaban (20 mg 1 time daily) and digoxin, which is a substrate of P-gp (0.25 mg 1 time daily), did not change the AUC or Cmax of digoxin. Thus, apixaban does not inhibit P-gp-induced substrate transport.
Naproxen. Concomitant administration of single doses of apixaban (10 mg) and the typical naproxen NSAID (500 mg) did not affect the AUC or Cmax of naproxen.
Atenolol. Concomitant administration of single doses of apixaban (10 mg) and the typical beta-blocker atenolol (100 mg) did not affect the pharmacokinetics of atenolol.
Dosage and administration
Method of application.
The drug is used orally. ELIQUIS should be taken with water, with or without food.
For patients who cannot swallow whole tablets, Eliquis tablets can be crushed and suspended in water, 5% aqueous dextrose solution or apple juice, or mixed with applesauce; then immediately apply the drug orally (see the section "pharmacokinetics"). Also, Eliquis tablets can be crushed and suspended in 60 ml of water or 5% aqueous dextrose solution and immediately administered through a nasogastric tube (see the section "pharmacokinetics").
Eliquis preparation in tablet form after grinding is stable in water, 5% aqueous dextrose solution, apple juice or applesauce for up to 4 hours.
Prevention of venous thromboembolism in the case of planned prosthetics of the knee or hip joint.
The recommended dose of ELIQUIS is 2.5 mg orally twice daily. The first dose should be taken 12-24 hours after surgery.
When choosing the time for the first administration of the drug within this window, doctors should consider the potential benefits of earlier initiation of anticoagulants for the Prevention of venous thromboembolism and the potential risk of postoperative bleeding.
For patients who have undergone hip replacement surgery, the recommended duration of treatment is 32-38 days, and for patients who have undergone knee replacement surgery – 10-14 days.
Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
The recommended dose of ELIQUIS is 5 mg orally twice daily.
For patients with non-Valve atrial fibrillation and at least two of the following characteristics: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL (133 mmol/L), the recommended dose of ELIQUIS is 2.5 mg orally twice daily.
Treatment should be carried out over a long period of time.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as prevention of relapses of DVT and PE.
The recommended dose of Eliquis for the treatment of DVT and PE is 10 mg orally twice daily for the first 7 days. Then the drug is used in a dosage of 5 mg orally twice a day. According to the current medical guidelines, a short duration of treatment (at least 3 months) should take into account the risk factors of passing (for example, recent surgery, trauma, immobilization).
Tags: Eliquis® [Apixaban]