Apyksaban | Elikvis tablets 2.5 mg, 20 pcs.
Special Price
$29.10
Regular Price
$37.00
In stock
SKU
BID468514
Release form
Film-coated tablets.
Film-coated tablets.
Release form
Film-coated tablets.
Packing
20 pcs.
Pharmacological action
Elikvis - direct-acting anticoagulant - a selective inhibitor of factor Xa blood coagulation.
The mechanism of action of apixaban is to inhibit the activity of FXa. As a result of this, apixaban changes the values of the indicators of the blood coagulation system: lengthens the prothrombin time, MHO and activated partial thromboplastin time (APTT). Changes in these indicators when using the drug in a therapeutic dose are insignificant and individual. Therefore, their use in order to assess the pharmacodynamic activity of apixaban is not recommended.
Apixaban inhibition of FXa activity was confirmed by a chromogenic test using Rotachrom heparin. The change in anti-FXa activity is directly proportional to the increase in the concentration of apixaban in blood plasma, while the maximum values of activity are observed when reaching Cmax of apixaban in blood plasma. A linear relationship between the 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 apixaban concentration are more pronounced and less variable than blood coagulation. The expected maximum and minimum anti-FXa activity of apixaban in equilibrium, when applied at a dose of 2.5 mg 2 times / day, is 1. 3MU / ml (5/95 percentile - 0.67 IU / ml - 2.4 IU / ml) and 0.84 IU / ml (5/95 percentile -0.37ME / ml-1. 8 IU / ml), respectively, which correlates with the fluctuations of this indicator in the interval between doses of the drug (less than 1.6 times). Against the background of apixaban therapy, routine monitoring of its concentration in blood plasma is not required, however, the Rotachrom anti-FXa activity test may be useful for deciding whether to continue therapy.
Indications
Prevention of venous thromboembolism in patients after elective hip or knee arthroplasty.
Contraindications
hypersensitivity to the active substance or auxiliary components
clinically significant active bleeding
liver disease, accompanied by disorders in the blood coagulation system and a clinically significant risk of bleeding
severe liver dysfunctions
creatinine impairment, less than 15 min kidney function as well as the use in patients undergoing
dialysis, it is not recommended to simultaneously take apixaban with drugs whose effect may be with associated with the development of severe bleeding
pregnancy
breastfeeding
age up to 18 years.
Precautions:
Risk of bleeding
As with other anticoagulants, careful monitoring of patients is necessary, taking ElikvisВ®, for the development of bleeding. The drug is recommended to be used with caution in conditions characterized by an increased risk of bleeding: congenital or acquired blood coagulation disorders, exacerbations of gastrointestinal ulcer conditions, bacterial endocarditis, thrombocytopenia, hemorrhagic stroke, a history of severe uncontrolled arterial hypertension, or recent surgical intervention or . If severe bleeding develops, ElikvisВ® should be discontinued.
With the development of hemorrhagic complications, the drug must be discontinued and screened to determine the source of bleeding. Consideration should also be given to the need for appropriate treatment, in particular surgical stopping of bleeding or transfusion of freshly frozen blood plasma.
Performing spinal, epidural anesthesia or punctures in patients receiving ElixisВ®
When performing spinal or epidural anesthesia or punctures of appropriate spaces in patients receiving antithrombotic agents to prevent thromboembolism, there is a risk of developing epidural or spinal hematomas, which in turn may cause persistent or irreversible paralysis. This risk may increase even more with the use of an installed epidural catheter in the postoperative period or with the parallel use of other drugs that affect hemostasis. Established epidural or subarachnoid catheters must be removed for at least 5 hours before the first dose of ElixisВ® is administered. A similar increase in risk can be observed when performing traumatic or multiple punctures of the epidural or subarachnoid spaces. Frequent monitoring of patients is necessary for the development of manifestations of impaired nervous system function (in particular, numbness or weakness of the lower extremities, impaired bowel or bladder function). With the development of such disorders, an emergency examination and treatment is necessary. Before performing interventions on epidural or subarachnoid spaces in patients receiving anticoagulants, including in order to prevent thrombosis, an assessment of the ratio of potential benefits and risks is necessary.
Surgery for hip fracture
In clinical trials, ElvisВ® was not used in patients who underwent surgery for a hip fracture, therefore its effectiveness and safety in this category of patients are unknown, and its use is not recommended.
Use during pregnancy and lactation
There is only limited information on the use of Elikvis® during pregnancy. The use of apixaban during pregnancy is not recommended.
There is no evidence of the excretion of apixaban or its metabolites in human breast milk. If it is necessary to use the drug Elikvis® during lactation, breastfeeding should be discontinued.
Special instructions
As with other anticoagulants, careful monitoring of patients taking Elikvis is necessary for the development of bleeding. With the development of severe bleeding, the drug Elikvis should be discontinued. With the development of hemorrhagic complications, it is necessary to cancel treatment with the drug and perform an examination to determine the source of bleeding. If necessary, appropriate treatment is prescribed, in particular surgical stopping of bleeding or transfusion of freshly frozen blood plasma.
Performing spinal, epidural anesthesia or puncture in patients receiving Eliquis
When performing spinal or epidural anesthesia or diagnostic puncture of these areas in patients receiving antithrombotic agents to prevent thromboembolism, there is a risk of developing epidural or spinal hematomas, which, in turn, may cause persistent or irreversible paralysis. This risk may increase even more with the use of an installed epidural catheter in the postoperative period or with the parallel use of other drugs that affect hemostasis. Installed epidural or subarachnoid catheters should be removed at least 5 hours before the first dose of Elikvis.
A similar increase in risk may occur with traumatic or multiple punctures of epidural or subarachnoid spaces. Frequent monitoring of patients is necessary for the development of manifestations of impaired nervous system function (in particular, numbness or weakness of the lower extremities, impaired bowel or bladder function). With the development of such disorders, an emergency examination and treatment is necessary. Before performing interventions on epidural or subarachnoid spaces in patients receiving anticoagulants, including in order to prevent thrombosis, an assessment of the ratio of potential benefits and risks is necessary.
Influence on the ability to drive vehicles and control mechanisms
Elikvis does not have a significant impact on the ability to drive a car and work with mechanisms.
Composition
1 tablet contains 2.5 mg apixaban.
Dosage and administration of
Inside, regardless of food intake (first intake, 12-24 hours after surgery), 1 tab. 2 times a day.
In patients undergoing hip replacement, the recommended duration of therapy is 32 to 38 days, of the knee 10 to 14 days.
If you miss a dose, you should take the drug as soon as possible, and continue to take it 2 times a day in accordance with the original scheme.
Use in patients with impaired renal function. In patients with impaired renal function, mild, moderate or severe (creatinine Cl - from 15 to 29 ml / min) dose adjustment is not required. Since there is no data on the use of the drug in patients with Cl creatinine® in this category of patients is not recommended.
Use in patients with impaired liver function. Elikvis® may be used with caution in patients with mild to moderate hepatic insufficiency (Child-Pugh class A or B). In patients suffering from impaired liver function of mild or moderate severity, dose adjustment of the drug is not required. The use of the drug in patients with severe hepatic insufficiency is not recommended.
Side effects
Adverse reactions were observed in 11% of patients receiving apixaban in a dose of 2.5 mg 2 times / day. As with other anticoagulants, bleeding can occur in patients with risk factors, such as organic damage associated with bleeding. The most common side effects were anemia, bleeding, bruising, and nausea. Adverse reactions developed in patients undergoing orthopedic surgery, on the background of apixaban therapy are presented below.
Further, the frequency of adverse reactions is understood: often -> 1/100, <1/10, infrequently -> 1/1000, <1/100, rarely -> 1/10000, <1/1000.
On the part of the blood and lymphatic system: often - anemia (including postoperative and posthemorrhagic, accompanied by corresponding changes in laboratory results) infrequently - thrombocytopenia (including a decrease in platelet count).
On the part of the immune system: rarely - hypersensitivity.
From the side of the organ of vision: rarely - hemorrhage in the tissue of the eyeball (including hemorrhage in the conjunctiva).
From the cardiovascular system: often - bleeding (including hematoma, vaginal and urethral bleeding) infrequently - arterial hypotension (including hypotension during the procedure).
From the respiratory system: infrequently - nosebleeds rarely - hemoptysis.
From the gastrointestinal tract: often - nausea infrequently - gastrointestinal bleeding (including vomiting mixed with blood and melena), the presence of unchanged blood in the feces rarely - rectal bleeding, bleeding from the gums.
From the liver and biliary tract: infrequently - increased transaminase activity (including increased ALT activity), increased AST activity, gamma-glutamyl transpeptidase, pathological changes in liver function tests, increased activity of alkaline phosphatase in the blood, increased bilirubin concentration in the blood.
From the musculoskeletal system: rarely - muscle hemorrhage.
From the urinary system: infrequently - hematuria (including the corresponding changes in the results of laboratory tests).
Other: often - closed trauma infrequently - hemorrhages and bleeding after performing invasive procedures (including hematoma after the procedure, bleeding from the postoperative wound, hematoma in the area of the puncture of the vessel and at the site of the catheter), discharge from the wound, hemorrhage in incision area (including hematoma in the incision area), bleeding during surgery.
Drug interactions
Effect of other drugs on the pharmacokinetics of apixaban
Inhibitors of CYP3A4 and P-glycoprotein
Combination of apixaban with ketoconazole (at a dose of 400 mg, 1 time per day), which is an increase in the rate of the potency of the 4 the average AUC of apixaban is 2 times and the average Cmax is 1.6 times. Dose adjustment of apixaban when combined 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 powerful inhibitors of CYP3A4 and P-glycoprotein.
drugs, moderately inhibiting the elimination of apixaban, CYP3A4 and / or P-glycoprotein is expected to lead to an increase in the concentration of apixaban in blood plasma to a lesser extent. For example, diltiazem (at a dose of 360 mg, 1 time per day), which is considered a moderate inhibitor of CYP3A4 and a weak inhibitor of P-glycoprotein, provided an increase in the average AUC of apixaban by 1.4 times and the average Cmax by 1.3 times.
Naproxen (at a dose of 500 mg), which is an inhibitor of P-glycoprotein, provided an increase in the average AUC and Cmax of apixaban by 1.5 and 1.6 times, respectively. At the same time, an increase in the values of the indicators of the blood coagulation system was noted. However, against the background of such a combination, there was no change in the effect of naproxen on platelet aggregation induced by arachidonic acid, and a clinically significant extension of bleeding time.
Dose adjustment of apixaban when combined with less active inhibitors of CYP3A4 and / or P-glycoprotein is not required.
Inducers of CYP3A4 and P-glycoprotein
Combining apixaban with rifampicin (a potent inducer of CYP3A4 and P-glycoprotein) led to a decrease in average AUC and Cmax of apixaban by approximately 54 and 42%, respectively. Therefore, the combination of apixaban with other powerful inducers of CYP3A4 and P-glycoprotein (in particular phenytoin, carbamazepine, phenobarbital or perforated hypericum preparations) can also lead to a decrease in the concentration of apixaban in blood plasma. Nevertheless, dose adjustment of apixaban when it is combined with the agents of this group is not required, however, these agents should be combined with caution.
Anticoagulants
After co-administration of enoxaparin (once, at a dose of 40 mg) and apixaban (once, at a dose of 5 mg), the additive effect of these agents on the activity of factor Xa was noted.
In view of the increased risk of bleeding, it is necessary to combine apixaban with other anticoagulants with caution.
Inhibitors of platelet aggregation and NSAIDs
No evidence of pharmacokinetic or pharmacodynamic interaction of apixaban with acetylsalicylic acid (325 mg, 1 time per day).
The combination of apixaban with clopidogrel (at a dose of 75 mg, 1 time per day) or a combination of clopidogrel (75 mg) and acetylsalicylic acid (162 mg, 1 time per day) did not lead to an increase in bleeding time, platelet aggregation, or indicators of the blood coagulation system ( PV INR and APTT) compared with the use of these antiplatelet agents in monotherapy.
Despite these data, it is possible to enhance the pharmacodynamic response to antiplatelet therapy when used in combination with apixaban. Therefore, caution should be exercised when combining it with NSAIDs (including acetylsalicylic acid) and / or platelet aggregation inhibitors, since these drugs usually increase the risk of bleeding.
Combination with other drugs
No clinically significant pharmacokinetic or pharmacodynamic interaction of apixaban with atenolol or famotidine has been identified. The combination of 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 the pharmacokinetics of apixaban, however, it was accompanied by a decrease in the average values of AUC and Cmax of apixaban by 15 and 18% than with its use in monotherapy. The combination of apixaban (at a dose of 10 mg) with famotidine (at a dose of 40 mg) did not affect the AUC or Cmax of apixaban.
Effect of apixaban on the pharmacokinetics of other drugs
In vitro studies have not revealed an inhibitory effect of apixaban on the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (IC50> has a weak inhibitory effect) and CYP2C19 (IC50> 20 μmol / L) in a concentration significantly higher than the Cmax of the drug in blood plasma during its clinical use.
Apixaban was not an inducer of CYP1A2, CYP2B6, CYP3A4 / 5 in concentrations up to 20 μmol / L. Therefore he is expected will not affect the metabolic clearance of drugs metabolized by these isoenzymes when used together. In addition, apixaban does not significantly inhibit the activity of P-glycoprotein.
In studies in healthy volunteers, apixaban did not significantly alter the pharmacokinetics of digoxin, naproxen, or atenolol.
digoxin. The combination of apixaban (at a dose of 20 mg, 1 time per day) and digoxin (at a dose of 0.25 mg, 1 time per day), which is a substrate of P-glycoprotein, did not affect the AUC or Cmax of digoxin. Therefore, apixaban does not inhibit the transport of P-glycoprotein substrates.
naproxen. The combination of apixaban (a single dose of 10 mg) and naproxen (500 mg), a commonly used NSAID, did not affect the AUC or Cmax of naproxen.
Atenolol. The combination of apixaban (a single dose of 10 mg) and atenolol (100 mg), a commonly used beta-blocker, did not affect the pharmacokinetics of the latter.
overdose
Symptoms: an overdose may increase the risk of bleeding. In controlled clinical trials, apixaban was administered orally to healthy volunteers at doses up to 50 mg / day for 3 to 7 days (25 mg twice daily for 7 days or 50 mg once daily for 3 days) 10 times above the maximum recommended dose for a person of clinically significant undesirable effects was not noted.
Treatment: Apixaban antidote is unknown. Preclinical studies have shown that that oral administration of activated charcoal within 3 h after oral administration of apixaban reduced the exposure values of apixaban, so in the case of overdose of this drug, consideration may be given to the use of activated charcoal.
Storage Conditions
The product should be stored out of the reach of children at a temperature not exceeding 25 РC.
active substance
apixaban
lekarstvennaja form
tablets
Prescribing
Adults as prescribed by a doctor
Indications
Indications
Prevention of stroke, Prevention of prophylaxis of thrombosis, thrombosis aktika acute myocardial infarction
Bristol-Myers Squibb Menyufekchuring Company, USA
Film-coated tablets.
Packing
20 pcs.
Pharmacological action
Elikvis - direct-acting anticoagulant - a selective inhibitor of factor Xa blood coagulation.
The mechanism of action of apixaban is to inhibit the activity of FXa. As a result of this, apixaban changes the values of the indicators of the blood coagulation system: lengthens the prothrombin time, MHO and activated partial thromboplastin time (APTT). Changes in these indicators when using the drug in a therapeutic dose are insignificant and individual. Therefore, their use in order to assess the pharmacodynamic activity of apixaban is not recommended.
Apixaban inhibition of FXa activity was confirmed by a chromogenic test using Rotachrom heparin. The change in anti-FXa activity is directly proportional to the increase in the concentration of apixaban in blood plasma, while the maximum values of activity are observed when reaching Cmax of apixaban in blood plasma. A linear relationship between the 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 apixaban concentration are more pronounced and less variable than blood coagulation. The expected maximum and minimum anti-FXa activity of apixaban in equilibrium, when applied at a dose of 2.5 mg 2 times / day, is 1. 3MU / ml (5/95 percentile - 0.67 IU / ml - 2.4 IU / ml) and 0.84 IU / ml (5/95 percentile -0.37ME / ml-1. 8 IU / ml), respectively, which correlates with the fluctuations of this indicator in the interval between doses of the drug (less than 1.6 times). Against the background of apixaban therapy, routine monitoring of its concentration in blood plasma is not required, however, the Rotachrom anti-FXa activity test may be useful for deciding whether to continue therapy.
Indications
Prevention of venous thromboembolism in patients after elective hip or knee arthroplasty.
Contraindications
hypersensitivity to the active substance or auxiliary components
clinically significant active bleeding
liver disease, accompanied by disorders in the blood coagulation system and a clinically significant risk of bleeding
severe liver dysfunctions
creatinine impairment, less than 15 min kidney function as well as the use in patients undergoing
dialysis, it is not recommended to simultaneously take apixaban with drugs whose effect may be with associated with the development of severe bleeding
pregnancy
breastfeeding
age up to 18 years.
Precautions:
Risk of bleeding
As with other anticoagulants, careful monitoring of patients is necessary, taking ElikvisВ®, for the development of bleeding. The drug is recommended to be used with caution in conditions characterized by an increased risk of bleeding: congenital or acquired blood coagulation disorders, exacerbations of gastrointestinal ulcer conditions, bacterial endocarditis, thrombocytopenia, hemorrhagic stroke, a history of severe uncontrolled arterial hypertension, or recent surgical intervention or . If severe bleeding develops, ElikvisВ® should be discontinued.
With the development of hemorrhagic complications, the drug must be discontinued and screened to determine the source of bleeding. Consideration should also be given to the need for appropriate treatment, in particular surgical stopping of bleeding or transfusion of freshly frozen blood plasma.
Performing spinal, epidural anesthesia or punctures in patients receiving ElixisВ®
When performing spinal or epidural anesthesia or punctures of appropriate spaces in patients receiving antithrombotic agents to prevent thromboembolism, there is a risk of developing epidural or spinal hematomas, which in turn may cause persistent or irreversible paralysis. This risk may increase even more with the use of an installed epidural catheter in the postoperative period or with the parallel use of other drugs that affect hemostasis. Established epidural or subarachnoid catheters must be removed for at least 5 hours before the first dose of ElixisВ® is administered. A similar increase in risk can be observed when performing traumatic or multiple punctures of the epidural or subarachnoid spaces. Frequent monitoring of patients is necessary for the development of manifestations of impaired nervous system function (in particular, numbness or weakness of the lower extremities, impaired bowel or bladder function). With the development of such disorders, an emergency examination and treatment is necessary. Before performing interventions on epidural or subarachnoid spaces in patients receiving anticoagulants, including in order to prevent thrombosis, an assessment of the ratio of potential benefits and risks is necessary.
Surgery for hip fracture
In clinical trials, ElvisВ® was not used in patients who underwent surgery for a hip fracture, therefore its effectiveness and safety in this category of patients are unknown, and its use is not recommended.
Use during pregnancy and lactation
There is only limited information on the use of Elikvis® during pregnancy. The use of apixaban during pregnancy is not recommended.
There is no evidence of the excretion of apixaban or its metabolites in human breast milk. If it is necessary to use the drug Elikvis® during lactation, breastfeeding should be discontinued.
Special instructions
As with other anticoagulants, careful monitoring of patients taking Elikvis is necessary for the development of bleeding. With the development of severe bleeding, the drug Elikvis should be discontinued. With the development of hemorrhagic complications, it is necessary to cancel treatment with the drug and perform an examination to determine the source of bleeding. If necessary, appropriate treatment is prescribed, in particular surgical stopping of bleeding or transfusion of freshly frozen blood plasma.
Performing spinal, epidural anesthesia or puncture in patients receiving Eliquis
When performing spinal or epidural anesthesia or diagnostic puncture of these areas in patients receiving antithrombotic agents to prevent thromboembolism, there is a risk of developing epidural or spinal hematomas, which, in turn, may cause persistent or irreversible paralysis. This risk may increase even more with the use of an installed epidural catheter in the postoperative period or with the parallel use of other drugs that affect hemostasis. Installed epidural or subarachnoid catheters should be removed at least 5 hours before the first dose of Elikvis.
A similar increase in risk may occur with traumatic or multiple punctures of epidural or subarachnoid spaces. Frequent monitoring of patients is necessary for the development of manifestations of impaired nervous system function (in particular, numbness or weakness of the lower extremities, impaired bowel or bladder function). With the development of such disorders, an emergency examination and treatment is necessary. Before performing interventions on epidural or subarachnoid spaces in patients receiving anticoagulants, including in order to prevent thrombosis, an assessment of the ratio of potential benefits and risks is necessary.
Influence on the ability to drive vehicles and control mechanisms
Elikvis does not have a significant impact on the ability to drive a car and work with mechanisms.
Composition
1 tablet contains 2.5 mg apixaban.
Dosage and administration of
Inside, regardless of food intake (first intake, 12-24 hours after surgery), 1 tab. 2 times a day.
In patients undergoing hip replacement, the recommended duration of therapy is 32 to 38 days, of the knee 10 to 14 days.
If you miss a dose, you should take the drug as soon as possible, and continue to take it 2 times a day in accordance with the original scheme.
Use in patients with impaired renal function. In patients with impaired renal function, mild, moderate or severe (creatinine Cl - from 15 to 29 ml / min) dose adjustment is not required. Since there is no data on the use of the drug in patients with Cl creatinine® in this category of patients is not recommended.
Use in patients with impaired liver function. Elikvis® may be used with caution in patients with mild to moderate hepatic insufficiency (Child-Pugh class A or B). In patients suffering from impaired liver function of mild or moderate severity, dose adjustment of the drug is not required. The use of the drug in patients with severe hepatic insufficiency is not recommended.
Side effects
Adverse reactions were observed in 11% of patients receiving apixaban in a dose of 2.5 mg 2 times / day. As with other anticoagulants, bleeding can occur in patients with risk factors, such as organic damage associated with bleeding. The most common side effects were anemia, bleeding, bruising, and nausea. Adverse reactions developed in patients undergoing orthopedic surgery, on the background of apixaban therapy are presented below.
Further, the frequency of adverse reactions is understood: often -> 1/100, <1/10, infrequently -> 1/1000, <1/100, rarely -> 1/10000, <1/1000.
On the part of the blood and lymphatic system: often - anemia (including postoperative and posthemorrhagic, accompanied by corresponding changes in laboratory results) infrequently - thrombocytopenia (including a decrease in platelet count).
On the part of the immune system: rarely - hypersensitivity.
From the side of the organ of vision: rarely - hemorrhage in the tissue of the eyeball (including hemorrhage in the conjunctiva).
From the cardiovascular system: often - bleeding (including hematoma, vaginal and urethral bleeding) infrequently - arterial hypotension (including hypotension during the procedure).
From the respiratory system: infrequently - nosebleeds rarely - hemoptysis.
From the gastrointestinal tract: often - nausea infrequently - gastrointestinal bleeding (including vomiting mixed with blood and melena), the presence of unchanged blood in the feces rarely - rectal bleeding, bleeding from the gums.
From the liver and biliary tract: infrequently - increased transaminase activity (including increased ALT activity), increased AST activity, gamma-glutamyl transpeptidase, pathological changes in liver function tests, increased activity of alkaline phosphatase in the blood, increased bilirubin concentration in the blood.
From the musculoskeletal system: rarely - muscle hemorrhage.
From the urinary system: infrequently - hematuria (including the corresponding changes in the results of laboratory tests).
Other: often - closed trauma infrequently - hemorrhages and bleeding after performing invasive procedures (including hematoma after the procedure, bleeding from the postoperative wound, hematoma in the area of the puncture of the vessel and at the site of the catheter), discharge from the wound, hemorrhage in incision area (including hematoma in the incision area), bleeding during surgery.
Drug interactions
Effect of other drugs on the pharmacokinetics of apixaban
Inhibitors of CYP3A4 and P-glycoprotein
Combination of apixaban with ketoconazole (at a dose of 400 mg, 1 time per day), which is an increase in the rate of the potency of the 4 the average AUC of apixaban is 2 times and the average Cmax is 1.6 times. Dose adjustment of apixaban when combined 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 powerful inhibitors of CYP3A4 and P-glycoprotein.
drugs, moderately inhibiting the elimination of apixaban, CYP3A4 and / or P-glycoprotein is expected to lead to an increase in the concentration of apixaban in blood plasma to a lesser extent. For example, diltiazem (at a dose of 360 mg, 1 time per day), which is considered a moderate inhibitor of CYP3A4 and a weak inhibitor of P-glycoprotein, provided an increase in the average AUC of apixaban by 1.4 times and the average Cmax by 1.3 times.
Naproxen (at a dose of 500 mg), which is an inhibitor of P-glycoprotein, provided an increase in the average AUC and Cmax of apixaban by 1.5 and 1.6 times, respectively. At the same time, an increase in the values of the indicators of the blood coagulation system was noted. However, against the background of such a combination, there was no change in the effect of naproxen on platelet aggregation induced by arachidonic acid, and a clinically significant extension of bleeding time.
Dose adjustment of apixaban when combined with less active inhibitors of CYP3A4 and / or P-glycoprotein is not required.
Inducers of CYP3A4 and P-glycoprotein
Combining apixaban with rifampicin (a potent inducer of CYP3A4 and P-glycoprotein) led to a decrease in average AUC and Cmax of apixaban by approximately 54 and 42%, respectively. Therefore, the combination of apixaban with other powerful inducers of CYP3A4 and P-glycoprotein (in particular phenytoin, carbamazepine, phenobarbital or perforated hypericum preparations) can also lead to a decrease in the concentration of apixaban in blood plasma. Nevertheless, dose adjustment of apixaban when it is combined with the agents of this group is not required, however, these agents should be combined with caution.
Anticoagulants
After co-administration of enoxaparin (once, at a dose of 40 mg) and apixaban (once, at a dose of 5 mg), the additive effect of these agents on the activity of factor Xa was noted.
In view of the increased risk of bleeding, it is necessary to combine apixaban with other anticoagulants with caution.
Inhibitors of platelet aggregation and NSAIDs
No evidence of pharmacokinetic or pharmacodynamic interaction of apixaban with acetylsalicylic acid (325 mg, 1 time per day).
The combination of apixaban with clopidogrel (at a dose of 75 mg, 1 time per day) or a combination of clopidogrel (75 mg) and acetylsalicylic acid (162 mg, 1 time per day) did not lead to an increase in bleeding time, platelet aggregation, or indicators of the blood coagulation system ( PV INR and APTT) compared with the use of these antiplatelet agents in monotherapy.
Despite these data, it is possible to enhance the pharmacodynamic response to antiplatelet therapy when used in combination with apixaban. Therefore, caution should be exercised when combining it with NSAIDs (including acetylsalicylic acid) and / or platelet aggregation inhibitors, since these drugs usually increase the risk of bleeding.
Combination with other drugs
No clinically significant pharmacokinetic or pharmacodynamic interaction of apixaban with atenolol or famotidine has been identified. The combination of 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 the pharmacokinetics of apixaban, however, it was accompanied by a decrease in the average values of AUC and Cmax of apixaban by 15 and 18% than with its use in monotherapy. The combination of apixaban (at a dose of 10 mg) with famotidine (at a dose of 40 mg) did not affect the AUC or Cmax of apixaban.
Effect of apixaban on the pharmacokinetics of other drugs
In vitro studies have not revealed an inhibitory effect of apixaban on the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (IC50> has a weak inhibitory effect) and CYP2C19 (IC50> 20 μmol / L) in a concentration significantly higher than the Cmax of the drug in blood plasma during its clinical use.
Apixaban was not an inducer of CYP1A2, CYP2B6, CYP3A4 / 5 in concentrations up to 20 μmol / L. Therefore he is expected will not affect the metabolic clearance of drugs metabolized by these isoenzymes when used together. In addition, apixaban does not significantly inhibit the activity of P-glycoprotein.
In studies in healthy volunteers, apixaban did not significantly alter the pharmacokinetics of digoxin, naproxen, or atenolol.
digoxin. The combination of apixaban (at a dose of 20 mg, 1 time per day) and digoxin (at a dose of 0.25 mg, 1 time per day), which is a substrate of P-glycoprotein, did not affect the AUC or Cmax of digoxin. Therefore, apixaban does not inhibit the transport of P-glycoprotein substrates.
naproxen. The combination of apixaban (a single dose of 10 mg) and naproxen (500 mg), a commonly used NSAID, did not affect the AUC or Cmax of naproxen.
Atenolol. The combination of apixaban (a single dose of 10 mg) and atenolol (100 mg), a commonly used beta-blocker, did not affect the pharmacokinetics of the latter.
overdose
Symptoms: an overdose may increase the risk of bleeding. In controlled clinical trials, apixaban was administered orally to healthy volunteers at doses up to 50 mg / day for 3 to 7 days (25 mg twice daily for 7 days or 50 mg once daily for 3 days) 10 times above the maximum recommended dose for a person of clinically significant undesirable effects was not noted.
Treatment: Apixaban antidote is unknown. Preclinical studies have shown that that oral administration of activated charcoal within 3 h after oral administration of apixaban reduced the exposure values of apixaban, so in the case of overdose of this drug, consideration may be given to the use of activated charcoal.
Storage Conditions
The product should be stored out of the reach of children at a temperature not exceeding 25 РC.
active substance
apixaban
lekarstvennaja form
tablets
Prescribing
Adults as prescribed by a doctor
Indications
Indications
Prevention of stroke, Prevention of prophylaxis of thrombosis, thrombosis aktika acute myocardial infarction
Bristol-Myers Squibb Menyufekchuring Company, USA
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