ELIQUIS 2.5MG PILLS
ELIQUIS 2.5MG PILLS - 60 tabs
Security policy (edit with Customer reassurance module)
Delivery policy (edit with Customer reassurance module)
Return policy (edit with Customer reassurance module)
1 pill contains apiksaban 2.5 mg
Mechanism of action
Direct acting anticoagulant is a selective inhibitor of blood coagulation factor Xa.
The mechanism of action of apixaban is to inhibit FXa activity. As a result, apixaban changes the values of the blood coagulation system: it extends the prothrombin time, MHO and activated partial thromboplastin time (APTT). Changes in these indicators when using the drug in a therapeutic dose are minor and individual. 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, and the maximum values of activity are observed when Cmax reaches apixaban in the blood plasma. 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 indicators.The expected maximum and minimum anti-FXa activity of apixaban in the equilibrium state, when used at a dose of 2.5 mg 2 times / day, is 1.ZME / 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 fluctuations of this indicator in the interval between doses of the drug (less than 1.6 times). The therapy with apixaban does not require routine monitoring of its concentration in the blood plasma, however, the execution of the Rotachrom anti-FXa test may be useful in deciding whether to continue therapy.
Indications and usage
- prevention of venous thromboembolism in patients after planned hip or knee arthroplasty;
- prevention of strokes, systemic thromboembolism and reduction in mortality in patients with atrial fibrillation. The exceptions are patients with severe and moderate mitral stenosis or artificial heart valves.
- hypersensitivity to any component of the drug;
- clinically significant bleeding;
- severe abnormal liver function;
- impaired renal function with Cl creatinine less than 15 ml / min, as well as use in patients on dialysis;
- age up to 18 years.
- It is not recommended to use apixaban at the same time with drugs that may be associated with the development of serious bleeding.
- Carefully: apixaban should be used with caution in patients with moderate and mild hepatic impairment (classes A or B according to the Child-Pugh classification); performing spinal / epidural anesthesia or spinal / epidural puncture (see "Special Instructions"); in patients receiving systemic therapy with potent inhibitors of CYP3A4 isoenzyme and P-glycoprotein, such as azole antifungal agents (in particular Ketoconazole, itraconazole, voriconazole, and posaconazole), HIV protease inhibitors (eg ritonavir); when using apixaban with potent inducers of CYP3A4 isoenzyme and P-glycoprotein (in particular, rifampicin, phenytoin, Carbamazepine, phenobarbital or Hypericum perforatum).
Pregnancy and breastfeeding
There is only limited information on the use of Eliquis during pregnancy. The use of apixaban during pregnancy is not recommended.
There is no information about the removal of apixaban or its metabolites in human breast milk. If necessary, the use of the drug Eliquis during lactation breastfeeding should be discontinued.
Dosage and administration
Inside regardless of the meal.
In case of skipping the drug should be taken as soon as possible, and then continue to receive 2 times a day in accordance with the original scheme.
In patients after planned hip or knee arthroplasty: 1 tab.2.5 mg 2 times a day (the first dose 12-24 hours after surgery).
In patients undergoing hip arthroplasty, the recommended duration of therapy is 32–38 days, the knee joint - 10–14 days.
In patients with atrial fibrillation: 1 tab. 5 mg 2 times a day.
Special patient groups
1. Patients with atrial fibrillation combined with two or more of the following characteristics. - age over 80 years, body weight less than 60 kg or plasma creatinine concentration ≥1.5 mg / dl (133 μmol / l) - the recommended dose of Eliquis is reduced to 1 tab. 2.5 mg 2 times a day.
2. Patients with impaired renal function. In case of impaired renal function, mild, moderate or severe, with a decrease in Cl of creatinine to 15 ml / min, dose adjustment of apixaban is not required (with the exception of patients indicated in paragraph 1). In patients with severe renal impairment with Cl creatinine less than 15 ml / min, as well as in patients on dialysis, the use of Eliquis is not recommended.
3. Patients with impaired liver function. Caution should be exercised when taking the drug Eliquis patients with mild to moderate hepatic insufficiency (class A or B according to the Child-Pugh classification), while dose adjustment is not required. Use of the drug in patients with severe liver failure is not recommended.
4. Elderly patients. Correction of the dose of the drug in elderly patients is not required (with the exception of patients referred to in paragraph 1).
5. Body weight. Dose adjustment depending on the patient's body weight is not required (with the exception of patients referred to in paragraph 1).
6. Paul. Correction of the dose of the drug depending on the gender of the patient is not required.
7. Race and ethnicity. Correction of the dose of the drug, depending on the race or ethnic origin of the patient is not required.
Transition from or to therapy with parenteral anticoagulants
A transfer from parenteral anticoagulants to the drug Eliquis and vice versa can be carried out at the time of the next scheduled administration of the drug being withdrawn (with the next dose of the drug being withdrawn not being taken).
Switching from or to Warfarin or other vitamin K antagonists
Transfer of patients with therapy with warfarin or other vitamin K antagonists to therapy with Eliquis® should be carried out with an INR value in a patient below 2.
When transferring patients from therapy with Eliquis® to warfarin or other vitamin K antagonists, therapy with Eliquis should be continued for 48 hours after taking the first dose of warfarin or other vitamin K antagonists.
Surgical and invasive procedures
Eliquis should be canceled 2-3 days before a planned surgery or invasive procedure. If it is not possible to postpone the procedure, special care should be taken, given the increased risk of bleeding. You should also evaluate the ratio of the risks of bleeding and postponing the operation.
Under the frequency of adverse reactions is understood: often - ≥1 / 100, <1/10; infrequently - ≥1 / 1000, <1/100; rarely - ≥1 / 10000, <1/1000.
Prevention of venous thromboembolism in patients after planned hip or knee arthroplasty
Adverse reactions were noted in 11% of patients who received apixaban at a dose of 2.5 mg 2 times a 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 have developed in patients undergoing orthopedic surgery, while being treated with apixaban, are presented below.
From the blood and lymphatic system: often - anemia (including postoperative and post-hemorrhagic, accompanied by corresponding changes in the results of laboratory tests), bleeding (including hematoma, vaginal and urethral bleeding); infrequently - thrombocytopenia (including platelet count reduction).
On the part of the immune system: rarely - hypersensitivity.
On the part of the organ of vision: rarely, hemorrhages in the tissue of the eyeball (including conjunctival bleeding).
From the CCC: infrequently - arterial hypotension (including hypotension during the procedure).
On the part of the respiratory system: infrequently - nosebleeds; rarely - hemoptysis.
From the digestive tract: 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.
Liver and biliary tract: infrequently - an increase in transaminase activity, incl. increased activity of ALT, AST, GGTP, pathological changes in liver function tests, increased activity of alkaline phosphorus cells in the blood, increased concentrations of bilirubin 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 studies).
Other: 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 (including drug hypersensitivity reactions, such as skin rash and Anaphylactic reactions, allergic edema).
From the nervous system: infrequently - intracranial hemorrhages, subarachnoid hemorrhages, subdural hematomas, hemorrhages in the spinal canal, spinal hematoma.
On the part of the organ of vision: often - hemorrhages in the tissue of the eyeball (including conjunctival hemorrhage).
From the CCC: often - other types of bleeding, hematoma; infrequently - bleeding into the abdominal cavity.
On the part of the respiratory system: often - nosebleeds; infrequently - hemoptysis; rarely, bleeding into the organs of the respiratory system (including pulmonary alveolar bleeding, laryngeal and pharyngeal bleeding).
From the digestive tract: 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 values: infrequently - a positive reaction in the analysis of feces on the hidden blood.
Other: often - closed injury; infrequently - traumatic bleeding, bleeding after the procedure, hemorrhage in the incision area.
In patients with atrial fibrillation and conditions requiring the use of monotherapy or therapy with a combination of two antiplatelet drugs, a thorough assessment of the benefit / risk ratio should be carried out before starting simultaneous use with Eliquis.
Eliquis is not recommended for use in patients with liver disease, accompanied by abnormalities in the blood coagulation system and a clinically significant risk of bleeding.
It was shown that in high-risk patients after acute coronary syndrome, with the presence of multiple cardiac and non-cardiac concomitant diseases, there was a significant increase in 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 the use of other anticoagulants, careful monitoring of patients taking Eliquis for the development of bleeding is necessary. With the development of severe bleeding, Eliquis should be withdrawn.
With the development of hemorrhagic complications, it is necessary to cancel the treatment with the drug and perform an examination to identify the source of bleeding. If necessary, appropriate treatment is prescribed, in particular, surgical treatment of hemorrhage or transfusion of fresh frozen plasma.
Cancel therapy with anticoagulants, incl. apixaban, with active bleeding before a planned surgery or invasive procedure can 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.
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 agents for the prevention of thromboembolism, there is a risk of developing epidural or spinal hematomas, which, in turn, may 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. 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 relationship between potential benefits and risks is necessary.
Influence on ability to drive vehicles and work with other mechanisms. Eliquis does not have a significant impact on the ability to drive a car and work with mechanisms.
Effect of other drugs on apixaban pharmacokinetics
Inhibitors of CYP3A4 and P-glycoprotein. The combination of apixaban with ketoconazole (at a dose of 400 mg, 1 time per day), which is a potent inhibitor of both CYP3A4 isoenzyme and P-glycoprotein, resulted in a 2-fold increase in the mean AUC value of apixaban and 1.6 times the average Cmax value. Dose adjustment of apixaban with its combination with ketoconazole is not required, but 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.
Drugs not related to the potent inhibitors of CYP3A4 isoenzyme and P-glycoprotein (for example, diltiazem, Naproxen, Amiodarone, Verapamil, quinidine) are likely to lead to an increase in plasma concentration of apixaban to a lesser extent. For example, diltiazem (a moderate inhibitor of the isoenzyme CYP3A4 and a weak inhibitor of P-glycoprotein) at a dose of 360 mg 1 time per day, led to an increase in mean AUC values of apixaban 1.4 times and average Cmax values 1.3 times. Naproxen (an inhibitor of P-glycoprotein) when used in a dose of 500 mg in healthy volunteers caused an increase in the mean AUC and Cmax values of apixaban by 1.5 and 1.6 times, respectively. At the same time, there was an increase in the values of blood coagulation system parameters (PV, MNO and APTT).However, no effect of naproxen on arachidonic acid-induced platelet aggregation, as well as clinically significant lengthening of bleeding time, was observed.
A dose adjustment of apixaban when combined with moderate inhibitors of the isoenzyme CYP3A4 and / or P-glycoprotein is not required.
Inductors of isoenzyme CYP3A4 and P-glycoprotein.The combination of apixaban 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 preparations) can also lead to a decrease in plasma concentration of apixaban. The dose adjustment of apixaban when combined with the means of this group is not required, however, these funds should be combined with caution.
Anticoagulants, inhibitors of platelet aggregation and NSAIDs . After co-administration of enoxaparin (once, at a dose of 40 mg) and apixaban (once, at a dose of 5 mg), an additive effect of these drugs on FXa activity was noted.
No signs of pharmacokinetic or pharmacodynamic interaction of apixaban with acetylsalicylic acid (at a dose of 325 mg, 1 time per day) were observed in healthy people.
Combining 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) in phase I of the clinical study did not lead to an increase in bleeding time or further inhibition of platelet aggregation compared with the use of these antiplatelet agents in monotherapy. Increased blood coagulation system (PW, INR and APTTV) corresponded to the effects of apixaban when used in monotherapy.
It is not recommended to use drugs that can be associated with the development of serious bleeding, such as unfractionated heparin or heparin derivatives (including low molecular weight heparins), oligosaccharides inhibiting FXa (eg fondaparinux), direct thrombin II inhibitors (eg desirudin), thrombolytic drugs, glycoprotein IIb / IIIa receptor antagonists, Dipyridamole, dextran, sulfinpyrazone, vitamin K antagonists and other oral anticoagulants. It should be noted that unfractionated heparin may be used in doses necessary to support the patency of the central venous or arterial catheter.
In patients after planned hip or knee arthroplasty, co-administration of apixaban with other antiplatelet agents or antithrombotic drugs is not recommended.
Combination with other drugs. No 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 the pharmacokinetics parameters of apixaban, but it was accompanied by a decrease in the mean AUC and Cmax-pixaban values by 15 and 18%, respectively, compared to the monotherapy regimen. The administration 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 researchin vitro apixaban did not inhibit the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6, or CYP3A4 isoenzymes (inhibitory concentration (IC50)> 45 µmol / L) and at the same time weakly suppressed the activity of the CYP2C19 isoenzyme (IC50> 20 µmol) and 20 µmol / mol / mol. significantly exceeding the Cmax 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. In studies in healthy volunteers, apixaban did not significantly alter the pharmacokinetics of Digoxin, naproxen or atenolol.
Symptoms: the risk of bleeding increases. In controlled clinical trials, apixaban was taken orally by healthy volunteers at doses up to 50 mg / day for 3–7 days (25 mg, 2 times a day for 7 days or 50 mg, 1 time per day for 3 days); no clinically significant adverse effects were noted.
Treatment: Consider the use of Activated carbon . Antidote drug is unknown.
At a temperature not higher than 30 ° C.