Eliquis pills 2.5 mg 60 pcs
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Apixaban
Release form
Pills
Composition
Active ingredient: Apixaban (Apixaban) Active substance concentration (mg): 2, 5
Pharmacological effect
Anticoagulant direct action, selective inhibitor of coagulation factor Xa (FXa). Apixaban is a potent direct inhibitor of FXa that reversibly and selectively blocks the active center of the enzyme. The drug is intended for oral administration. To implement the antithrombotic activity of apixaban, antithrombin III is not required. Apixaban inhibits free and bound FXa, as well as prothrombinase activity. Apixaban does not directly affect platelet aggregation, but indirectly inhibits thrombin-induced platelet aggregation. By inhibiting the activity of FXa, apixaban prevents the formation of thrombin and blood clots. As a result of the suppression of FXa, the values of the blood coagulation system parameters change: the prothrombin time is prolonged, the APTT is increased, and an increase in INR occurs. Changes in these indicators with the use of the drug in a therapeutic dose are insignificant and largely variable. Therefore, using them to assess the pharmacodynamic activity of apixaban is not recommended. Inhibiting FXa activity with apixaban has been proven using a chromogenic test using Heparin Rotachrom. The change in anti-FXa activity is directly proportional to the increase in the concentration of apixaban in the blood plasma, while the maximum activity values are observed when the maximum concentration of apixaban in the blood plasma is reached. The linear relationship between concentration and anti-FXa activity of apixaban is recorded in a wide range of therapeutic doses of the drug. Changes in anti-FXa activity with changes in dose and concentration of apixaban are more pronounced and less variable than blood clotting rates.
Pharmacokinetics
Absorption When using apixaban in doses up to 10 mg, its absolute bioavailability reaches 50%. Apixaban is rapidly absorbed from the gastrointestinal tract, Cmax is achieved within 3-4 hours after oral administration. Eating does not affect the AUC or Cmax values of apixaban. The pharmacokinetics of apixaban for doses up to 10 mg is linear.When taking apixaban in doses higher than 25 mg, the absorption of the drug is limited, which is accompanied by a decrease in its bioavailability. Metabolism indicators of apixaban are characterized by low or moderate inter-and intraindividual variability (the corresponding values of the coefficient of variation are approximately 20% and 30%, respectively). DistributionBinding of apixaban to human plasma proteins is approximately 87%, Vss is approximately 21 l. Metabolism and elimination Approximately 25% The dose taken is excreted as metabolites. The main route of elimination is through the intestines. The renal excretion of apixaban is approximately 27% of its total clearance. The total clearance of apixaban is approximately 3.3 l / h, T1 / 2 is about 12 hours. O-demethylation and hydroxylation at the 3-oxopiperidinyl balance are the main ways of biotransformation of apixaban. Apixaban is predominantly metabolized by the participation of the CYP3A4 / 5 isoenzyme, and to a lesser extent by the CYP1A2, 2C8, 2C9, 2C19 and 2J2 isoenzymes. Unchanged apixaban is the main substance circulating in human blood plasma, there are no active metabolites circulating in the bloodstream. In addition, apixaban is a substrate of transport proteins, P-glycoprotein and breast cancer resistance protein (BCRP). Pharmacokinetics in special clinical situationsDisruption of renal function does not affect Cmax of apixaban. However, there was an increase in the concentration of apixaban, which correlated with the degree of decline in renal function, as measured by CC values. In persons with impaired lung function of the kidneys (CC - from 51 ml / min to 80 ml / min), medium (CC - from 30 ml / min to 50 ml / min) and severe (CC - from 15 ml / min to 29 ml / min) degree, the AUC values of apixaban in the blood plasma increased by 16%, 29% and 44%, respectively, compared with persons who had normal CC values. At the same time, renal impairment did not have an obvious effect on the relationship between plasma concentration of apixaban and its anti-FXa activity. Studies of apixaban in patients with QA <15 ml / min or on dialysis have not been conducted. Violation of the liver. Studies of apixaban in severe liver failure and active pathology of the hepatobiliary system have not been conducted. There were no significant changes in pharmacokinetic and pharmacodynamic parameters with a single dose of apixaban at a dose of 5 mg in patients with mild to moderate hepatic insufficiency (classes A and B according to Child-Pugh, respectively) compared with healthy volunteers.Changes in anti-FXa activity and INR in patients with mild to moderate hepatic insufficiency and healthy volunteers were comparable. Older patients (over 65) had higher plasma concentrations of the drug than younger patients: mean AUC was approximately 32% higher. Pol. Exposure of apixaban in women was 18% higher than in men. Rasa and ethnic origin. The results obtained in the framework of studies of phase 1 indicate the absence of significant differences in apixaban pharmacokinetics between representatives of the Caucasoid, Mongoloid, and Negroid races. The results of pharmacokinetics analyzes in various populations performed as part of studies that included patients who received apixaban after planned hip or knee arthroplasty correspond to the results of phase 1 studies. Body mass. In patients with a body weight of more than 120 kg, the concentration of apixaban in the blood plasma was approximately 30% lower than in patients with a body weight from 65 kg to 85 kg; in patients weighing less than 50 kg, this indicator was approximately 30% higher. Dependence of pharmacokinetic and pharmacodynamic parameters The relationship between pharmacokinetic and pharmacodynamic parameters (including anti-FXa activity, MHO, prothrombin time, APTT) of apixaban and its concentration in Blood plasma has been studied for a wide range of drug doses (from 0.5 mg to 50 mg). It was shown that the relationship between apixaban concentration and FXa activity is best described using a linear model. The dependence of the pharmacokinetics and pharmacodynamics parameters of apixaban, assessed in patients receiving apixaban in phase 2 and 3 clinical trials, was consistent with that in healthy volunteers.
Indications
Prevention of venous thromboembolism in patients after planned hip or knee arthroplasty; prevention of stroke and systemic thromboembolism in adult patients with non-valvular atrial fibrillation with one or several risk factors (such as a stroke or a transient ischemic attack in history, age 75 years and older, arterial hypertension, diabetes mellitus, accompanied by symptoms of chronic heart failure (functional class II and NYHA classification)).The exceptions are patients with severe and moderately pronounced mitral stenosis or with artificial heart valves; treatment of deep vein thrombosis (THV), pulmonary thromboembolism (PE), and the prevention of recurrent DVT and PE.
Contraindications
Clinically significant bleeding - conditions characterized by an increased risk of bleeding: congenital or acquired bleeding disorders; acute gastrointestinal ulcer; bacterial endocarditis; thrombocytopenia; thrombocytopathy; hemorrhagic stroke in history; recent surgery on the brain or spinal cord, as well as on the organ of vision; severe uncontrolled arterial hypertension; severe liver dysfunction, liver disease, accompanied by disorders in the blood coagulation system and a clinically significant risk of bleeding; kidney dysfunction with a CC of less than 15 ml / min, and use in dialysis patients; simultaneous use with drugs whose action may be associated with the development of serious bleeding, such as any anticoagulant drugs, unfractionated heparins, low molecular weight heparins (enox aparin, dalteparin), heparin derivatives (fondaparinux), oral anticoagulants (warfarin, rivaroxaban, dabigatran), with the exception of situations when the patient is transferred to therapy with apixaban therapy or if unfractionated heparin is administered in doses necessary to maintain central venous patency or arterial catheter (see section Drug Interactions); - pregnancy (data on the use of the drug are not available); - breastfeeding (data on the use of the drug are not available); - detsk and adolescence to 18 years of age (data on the use of the drug are not available) - congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption; - hypersensitivity to any component of the drug.
Precautionary measures
Experience with the use of the drug with thrombolytic agents for the relief of acute ischemic stroke is limited. Apiksaban should be used with caution in patients with impaired liver function of moderate and mild severity (grades A or B according to Child-Pugh classification). Apiksaban should be used withcaution when performing spinal / epidural anesthesia or spinal / epidural puncture, as well as in patients receiving systemic therapy with potent inhibitors of the CYP3A4 isoenzyme and P-glycoprotein, such as azole antifungal agents (such as ketoconazole, itraconazole, voriconazole and eye cream, for example, azole antifungal agents (in particular, ketoconazole, itraconazole, voriconazole and eye antifungal agents (in particular, ketoconazole, itraconazole, voriconazole and eye cream) HIV (for example, ritonavir). You should also be careful when using apixaban with potent inducers of CYP3A4 isoenzyme and P-glycoprotein (in particular, rifampicin, phenytoin, carbamazepine, phenobarbital or Hypericum perforatum drugs). It is not recommended to use the drug in liver diseases that are accompanied by disorders in the blood clotting system and there are no changes in the system of coagulation of the blood and the heart in the system. risk of bleeding. It is necessary to stop the use of the drug in the event of severe bleeding. In the event of a complication in the form of bleeding, drug therapy should be stopped; it is also necessary to establish the source of the bleeding. Among the possible options for stopping bleeding, surgical hemostasis or transfusion of fresh frozen plasma, in life-threatening conditions that cannot be controlled using the above methods, may be considered, it is possible to consider the introduction of recombinant coagulation factor VIIa, although the experience of using this coagulation factor in patients receiving apixaban therapy , at the moment there is no. Care should be taken with simultaneous use of apixaban with NSAIDs (including with ats tilsalitsilovoy acid), due to the fact that these drugs increase the risk of developing clinical trials krovotecheniy.V Eliquis not be used in patients undergoing emergency surgery for a hip fracture, so its efficacy and safety in these patients has not been studied.
Use during pregnancy and lactation
During preclinical studies revealed no toxicity of the drug in relation to reproductive function. There is limited information on the use of the drug Eliquis during pregnancy. The use of apixaban during pregnancy is not recommended. In studies in rats, the concentration of the drug in breast milk was many times higher than that in plasma (Cmax is about 8 times higher, AUC is about 30 times higher), which may indicate an active transport of the drug in breast milk. The risk for breastfed babies cannot be excluded.There is no information about the removal of apixaban or its metabolites in human breast milk. If you need to use the drug Eliquis during lactation, breastfeeding should be discontinued. The effect on fertility Apixaban did not affect fertility in animal studies.
Dosage and administration
The drug Eliquis is taken orally, regardless of the meal. In case of missing a dose, the drug should be taken as soon as possible, and then continue to receive it 2 times / day in accordance with the original scheme.
Side effects
Prevention of venous thromboembolism in patients after planned hip or knee arthroplasty. Undesirable reactions were observed in 11% of patients who received apixaban at a dose of 2.5 mg 2 times / day. As with other anticoagulants, bleeding can occur in patients with risk factors, such as organic lesions, which may be accompanied by bleeding. The most frequent side effects were anemia, bleeding, hematomas, nausea. The adverse reactions that developed in patients undergoing orthopedic surgery during therapy with apixaban are presented below. From the blood and lymphatic system: often anemia (including postoperative and post-hemorrhagic, accompanied by appropriate changes in laboratory results), bleeding (in including hematoma, vaginal and urethral bleeding); infrequently - thrombocytopenia (including platelet count reduction). From the immune system: rarely - hypersensitivity. From the organ of vision: rarely - hemorrhages in the tissue of the eyeball (including hemorrhage into the conjunctiva). From the side of the heart vascular system: infrequently - arterial hypotension (including hypotension during the procedure). On the part of the respiratory system: infrequently - nosebleeds; rarely - hemoptysis. From the digestive system: often - nausea; infrequently - gastrointestinal bleeding (including vomiting with blood and melena), the presence of unchanged blood in the feces; rarely - rectal bleeding, bleeding from the gums. From the side of the liver and biliary tract: infrequently - an increase in the activity of transaminases, incl. increased activity of ALT, AST, GGT, pathological changes in liver function tests, increased activity of alkaline phosphatase in the blood, increased concentration of bilirubin in the blood. From the musculoskeletal system: rarely - muscle hemorrhage. From the urinary system: infrequently - hematuria (in t. hrelevant changes in laboratory results). Others: often - closed injury; infrequently - hemorrhages and bleeding after performing invasive procedures (including hematoma after the procedure, bleeding from a postoperative wound, hematoma in the area of vessel puncture and at the catheter site), the presence of discharge from the wound, hemorrhage in the area of the incision (including hematoma in the incision area), bleeding during surgery. Prevention of stroke and systemic embolism in patients with atrial fibrillation. On the part of the immune system: infrequently - hypersensitivity such as skin rashes, anaphylactic reactions and allergic edema). On the nervous system: infrequently - intracranial hemorrhages, subarachnoid hemorrhages, subdural hematomas, hemorrhages in the spinal canal, spinal hematoma. (including conjunctival hemorrhage). From the cardiovascular system: often - other types of bleeding, hematomas; infrequently - bleeding into the abdominal cavity. On the part of the respiratory system: often - nosebleeds; infrequently - hemoptysis; rarely - bleeding in the respiratory system (including pulmonary alveolar bleeding, laryngeal and pharyngeal bleeding). From the digestive system: often - gastrointestinal bleeding (including vomiting with blood and melena), rectal bleeding ; bleeding from the gums; infrequently - hemorrhoidal bleeding, the presence of unchanged blood in the feces, bleeding in the oral cavity; rarely - retroperitoneal hemorrhage. From the urinary system: often - hematuria. From the reproductive system: infrequently - intermenstrual vaginal bleeding, urogenital bleeding. Reactions at the injection site: infrequently - bleeding at the injection site. Laboratory parameters: infrequent - positive reaction in the analysis. for hidden blood. Others: often - closed injury; infrequently - traumatic bleeding, bleeding after the procedure, hemorrhage in the incision area. Treatment of deep vein thrombosis, pulmonary embolism: On the side of the blood and lymphatic system: rarely - hemorrhagic anemia,hemorrhagic diathesis, spontaneous hematomas. From the nervous system: rarely - cranial hemorrhages, hemorrhagic stroke. From the organ of vision: infrequently - conjunctival hemorrhage; rarely - hemorrhages in the tissue of the eyeball, hemorrhages in the retina, sclera, vitreous body. On the part of the ear: rarely - ear bleeding. On the part of the cardiovascular system: often - hematomas; rarely - pericardial bleeding, other types of bleeding, bleeding into the abdominal cavity, hemorrhagic shock. On the part of the respiratory system: often - nosebleeds; infrequently - hemoptysis; rarely - pulmonary alveolar bleeding. From the side of the gastrointestinal tract: often - bleeding from the gums; infrequently - rectal bleeding, the presence of unchanged blood in the feces, hemorrhoidal bleeding, gastrointestinal bleeding, bloody vomiting; rarely - melena, anal bleeding, bleeding from gastric and duodenal ulcers, bleeding into the oral cavity, abdominal wall hematomas, Mallory-Weiss syndrome, gastric bleeding, bleeding in the small intestine. On the skin side: infrequently - bleeding, bleeding from the intestines. ; rarely - petechiae, purpura, increased tendency to bleeding, blood callus, bleeding from skin ulcers. On the part of the musculoskeletal system: rarely - hemorrhage into muscles. On the part of the urinary system: often - hematuria; rarely, urinary system hemorrhage. From the reproductive system: often hypermenorrhea; infrequently - vaginal bleeding, metrorrhagia; rarely - menometrorragia, uterine bleeding, genital bleeding, hemorrhages in the mammary gland, hematospermia, uterine bleeding after menopausal. traumatic hematoma; rarely - bleeding at the injection site, hematoma at the infusion site, periorbital hematoma, vascular pseudoaneurysm, subcutaneous hematoma, hematoma during and after the procedure, hematuria after the procedure, extradural hematoma, subdural hemorrhage, kidney hematoma. blood in the urine, a positive reaction in the analysis of fecal occult blood; rarely - hidden blood, the presence of red blood cells in the urine.
Overdose
Overdose increases the risk of bleeding.In controlled clinical studies, apixaban was taken orally by healthy volunteers at doses up to 50 mg / day for 3 to 7 days (25 mg 2 times / day for 7 days or 50 mg 1 time / day for 3 days); no clinically significant adverse effects were noted. Treatment: in case of an overdose of this drug, the use of activated carbon can be considered. When administered to healthy volunteers, activated carbon 2 and 6 hours after taking apixaban at a dose of 20 mg, the AUC for apixaban decreased by 50% and 27%, respectively (Cmax did not change). T1 / 2 apixaban decreased from 13.4 to 5.3 and 4.9 h, respectively. The antidote is not known. It is not expected that the use of hemodialysis in overdose of apixaban will be an effective measure.
Interaction with other drugs
The effect of other drugs on the pharmacokinetics of apixaban CYP3A4 isoenzyme inhibitors and P-glycoprotein The combination of apixaban with ketoconazole (400 mg, 1 time / day), a potent inhibitor of both CYP3A4 isoenzyme and P-glycoprotein, has increased the level of the headline, it has improved, and the average value of Cmax - 1.6 times. Dose adjustment of apixaban with its combination with ketoconazole is not required, however, apixaban should be used with caution in patients receiving systemic therapy with azole antifungal agents, in particular ketoconazole, or other potent inhibitors of the CYP3A4 isoenzyme and P-glycoprotein. with rifampicin (a potent inducer of CYP3A4 isoenzyme and P-glycoprotein) resulted in a decrease in the mean AUC and Cmax values of apixaban by approximately 54% and 42%, respectively. Apparently, the combination of apixaban with other potent inducers of the CYP3A4 isoenzyme and P-glycoprotein (in particular, phenytoin, carbamazepine, phenobarbital or St. John's wort) can also lead to a decrease in the concentration of apixaban in the blood plasma (approximately 50%). Dose adjustment apixaban when combined with the means of this group is not required when assigning indications: prevention of thromboembolism after hip replacement joints, prevention of stroke and systemic embolism with non-valvular atrial fibrillation and relapse prevention of deep vein thrombosis, pulmonary embolism, but to combine these agents with caution .During use for the treatment of deep vein thrombosis and pulmonary embolism, the combined use of apixaban and powerful inducers of the CYP3A4 isoenzyme and P-glycoprotein is not recommended. 5 mg) an additive effect of these agents on FXa activity was noted. Signs of pharmacokinetic or pharmacodynamic interaction of apixaban with acetylsalicylic acid (at a dose of 325 mg 1 time / day) in healthy people There was no recommendation. It is not recommended to use drugs that may be associated with the development of serious bleeding, such as unfractionated heparin or heparin derivatives (including low molecular weight heparins), FXa inhibitory oligosaccharides (for example, fondaparinux), direct thrombin II inhibitors (for example, desirudin), thrombolytic drugs, glycoprotein IIb / IIIa receptor antagonists, dipyridamole, dextran, sulfinpyrazon, vitamin K antagonists and other oral anticoagulants. It should be noted that unfractionated heparin may be used in doses necessary to maintain the patency of a venous or arterial catheter. In patients after a planned hip or knee joint endoprosthetics, co-administration of apixaban with other antiplatelet agents or other antithrombotic drugs is not recommended. Combination with other drugsNo clinically significant pharmacokinetic or pharmacodynamic interaction of apixaban with atenolol or famotidine was detected. Combining apixaban (at a dose of 10 mg) with atenolol (at a dose of 100 mg) did not lead to the development of clinically significant changes in apixaban pharmacokinetics parameters, however, it was accompanied by a decrease in the mean AUC and Cmax values of apixaban by 15% and 18%, respectively, compared to the monotherapy regimen. Appointment of apixaban (at a dose of 10 mg) with famotidine (at a dose of 40 mg) did not affect the AUC or Cmax values of apixaban. The effect of apixaban on the pharmacokinetics of other drugs In in vitro studies, apixaban did not inhibit the activity of CYP1A2, CYP2A6, CYP2B6, CYP2 isoenzymes. , CYP2D6 or CYP3A4 (inhibitory concentration (IC50)> 45 μmol / l), however, weak suppression of the activity of the CYP2C19 isoenzyme (IC50> 20 μmol / l) by apixaban was found at a concentration significantly exceeding Cmax of the drug in blood plasma during its clinical use.Apixaban is not an inducer of CYP1A2, CYP2B6, CYP3A4 / 5 isoenzymes in concentrations up to 20 µmol / L. In this regard, it is expected that when used together, it will not affect the clearance of drugs metabolized by these isoenzymes. In addition, apixaban does not significantly inhibit the activity of P-glycoprotein.
special instructions
Risk of bleeding Patients with atrial fibrillation and conditions requiring monotherapy or therapy with a combination of two antiplatelet drugs should be carefully assessed for the benefit / risk ratio before starting simultaneous use with Eliquis. Eliquis is not recommended for patients with liver disease that is accompanied by impaired system blood coagulation and a clinically significant risk of bleeding. In high-risk patients after acute coronary syndrome, with the presence of m Both cardiac and non-cardiac comorbidities have been shown to significantly increase the risk of bleeding with the combined use of apixaban and acetylsalicylic acid or a combination of acetylsalicylic acid and clopidogrel compared with placebo. As with other anticoagulants, careful monitoring of patients taking Eliquis is necessary, for the development of bleeding. With the development of severe bleeding, taking Eliquis should be discontinued. With the development of hemorrhagic complications, treatment with the drug should be discontinued and an examination should be carried out to determine the source of bleeding. If necessary, appropriate treatment is prescribed, in particular, surgical treatment of hemorrhage or transfusion of fresh frozen plasma. Cancellation of anticoagulant therapy, including apixaban, with active bleeding, before a planned surgical intervention or an invasive procedure, may lead to an increased risk of thrombosis. Long-term cessation of therapy should be avoided and, if it is necessary to temporarily stop apixaban therapy, it should be resumed as soon as possible. Remedial interventions related to hip fracture Within the framework of clinical studies, Eliquis was not used in patients undergoing emergency surgery for a hip fracture,thus, the efficacy and safety of this category of patients has not been studied. Performing spinal, epidural anesthesia or punctures in patients receiving Eliquis When performing spinal or epidural anesthesia or diagnostic puncture of these areas in patients receiving antithrombotic drugs for the prevention of thromboembolism, there is a risk of developing epidural or spinal hematomas, which, in turn, can cause persistent or irreversible paralysis. This risk may further increase with the use of an established epidural catheter in the postoperative period or with the simultaneous use of other drugs that affect hemostasis. Installed epidural or subarachnoid catheters should be removed at least 5 hours prior to the first dose of Eliquis. There is no clinical experience with apixaban in patients with an established intrathecal or epidural catheter. If this situation is necessary, based on the pharmacokinetic features of apixaban, an interval of 20-30 hours (ie, 2 T1 / 2) between the last dose of apixaban and catheter removal should be observed, so at least one dose of apixaban should be missed. before the catheter is removed. A similar increase in risk may be observed when traumatic or repeated punctures of the epidural or subarachnoid spaces are performed. Frequent monitoring of patients for the development of manifestations of impaired function of the nervous system (in particular, numbness or weakness of the lower extremities, impaired function of the intestine or bladder) is necessary. With the development of such disorders, it is necessary to perform an emergency examination and treatment. Before performing interventions on epidural or subarachnoid spaces in patients receiving anticoagulants, incl. in order to prevent thrombosis, an assessment of the ratio of potential benefits and risks is needed. Patients with cardiac valve valves. The safety and efficacy of the drug in patients with cardiac valve valves with atrial fibrillation and without it has not been studied. The use of Eliquis for this group of patients is not recommended. Treatment of deep vein thrombosis and TELANE is recommended to replace therapy with nefractionated heparin with Eliquis during the initiation of therapy for patients with pulmonary embolism with unstable hemodynamics,possible carrying out of a thrombolysis or a thrombectomy of a pulmonary artery. Influence on ability to driving of motor transport and management of mechanismsEliquis does not exert essential impact on ability to control motor transport and work with mechanisms.