Eliquis 2.5mg pills №20

Indications and usage

- 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 chronic heart failure symptoms ( functional class II and higher according to the 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 prevention of recurrent DVT and PE.

Dosing regimen Eliquis

Drug Eliquis^® ingested, regardless of the meal.

In case of skipping the drug should be taken as soon as possible, and then continue to receive 2 times / day in accordance with the original scheme.

After routine hip or knee arthroplasty prescribed 2.5 mg 2 times / day (the first admission after 12-24 h after surgery). In patients undergoing hip arthroplasty, the recommended duration of therapy is 32 to 38 days, and the knee joint is 10 to 14 days.

Atrial fibrillation patients prescribe 5 mg 2 times / day.A dosage of 2.5 mg (2.5 mg tablet) is used when there is a combination of two or more of the following characteristics: age 80 years and older, body weight 60 kg or less, or plasma creatinine concentration ≥ 1.5 mg / dl (133 μmol / l).

For the treatment of deep vein thrombosis, pulmonary thromboembolism (PE) appoint 10 mg 2 times / day for 7 days, then 5 mg 2 times / day. The duration of treatment is determined individually, taking into account the ratio of the expected benefit and the risk of clinically significant bleeding. The decision on the duration of therapy should be based on an assessment of the presence and reversibility of factors predisposing to recurrence (i.e., prior surgery, trauma, immobilization period, etc.), as well as manifestations of DVT and / or pulmonary embolism, making at least 3 months.

For the prevention of recurrent deep vein thrombosis, pulmonary thromboembolism (PE) prescribed 2.5 mg 2 times / day after at least 6 months of treatment of deep vein thrombosis or pulmonary embolism.

At renal dysfunction mild, moderate or severe with a CC ≥ 15 ml / min dose adjustment of apixaban is not required. In patients with severe renal dysfunction with CC <15 ml / min, as well as in patients on dialysis, the use of the drug Eliquis^® Not recommended.

Care should be taken when taking Eliquis^® patients with liver failure easy and moderate severity (class A or B according to Child-Pugh classification), while dose adjustment is not required. Use of the drug Eliquis in patients with severe hepatic impairment is not recommended.

Correction dose of the drug Eliquis in patients old age not required (except for patients with atrial fibrillation).

Dose adjustment depending on body mass the patient is not required (except for patients with atrial fibrillation).

Dose adjustment of the drug Eliquis depending on the floor no patient required.

Dose adjustment of the drug Eliquis depending on race or ethnicity no patient required.

Transition from or to therapy with parenteral anticoagulants

Translation from parenteral anticoagulants to Eliquis^® and vice versa, it can be performed at the time of the next scheduled intake 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 when the INR value of the patient is below 2.0.

When transferring patients from therapy with Eliquis^® for warfarin or other vitamin K antagonists, Eliquis should continue therapy^® within 48 hours after taking the first dose of warfarin or other vitamin K antagonists. After 48 hours, check the INR before taking the next dose of Eliquis^®. Combined use of warfarin (or another vitamin K antagonist) and Eliquis^® should continue until an INR ≥ 2.0 is reached. When an INR ≥ 2.0 is reached, taking Eliquis^® should stop.

Surgical and invasive procedures

Elikvis^® should be canceled at least 48 hours before a planned surgery or invasive procedure with an estimated average or high risk of life threatening or clinically significant bleeding. Eliquis^® should be canceled at least 24 hours before a planned surgery or an invasive procedure if there is a low risk of bleeding or if noncritical localization is possible, which can be easily controlled. 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.

In non-valvular atrial fibrillation, it is usually not necessary to use a “bridge therapy” within 24-48 hours after discontinuation of apixaban before surgery.

Post-intervention apixaban therapy should be resumed immediately after adequate hemostasis is achieved.

Patients may continue taking Eliquis.^® during cardioversion.

With a temporary interruption in the treatment with Eliquis (accidental or deliberate), the risk of thrombosis increases. Patients should be instructed to avoid interruptions in treatment with Eliquis. With temporary suspension of anticoagulation therapy for any reason, it should be resumed as soon as possible.

Side Effects of Eliquis

Determination of the frequency of adverse reactions: often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10 000, <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 / 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.

Blood and lymphatic system: Often - anemia (including postoperative and post-hemorrhagic, accompanied by corresponding changes in laboratory results), bleeding (including hematoma, vaginal and urethral bleeding); infrequently - thrombocytopenia (including platelet count reduction).

Immune system: rarely - hypersensitivity.

Special senses: rarely, hemorrhages in the tissue of the eyeball (including conjunctival bleeding).

Cardiovascular: infrequently - arterial hypotension (including hypotension during the procedure).

Respiratory: infrequently - nosebleeds; rarely - hemoptysis.

Gastrointestinal: 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, GGT, pathological changes in liver function tests, increased activity of alkaline phosphatase in the blood, increased concentration of bilirubin in the blood.

Musculoskeletal system: rarely - muscle hemorrhage.

Urogenital: 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

Immune system: infrequently, hypersensitivity (including drug hypersensitivity reactions, such as skin rash, Anaphylactic reactions and 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).

Since the cardiovascular system: often - other types of bleeding, hematoma; infrequently - bleeding into the abdominal cavity.

On the part of the respiratory system: often - nose bleed; infrequently - hemoptysis; rarely, bleeding into the organs of the respiratory system (including pulmonary alveolar bleeding, laryngeal and pharyngeal bleeding).

Gastrointestinal: 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; seldom - 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.

Treatment of deep vein thrombosis, pulmonary thromboembolism

From the blood and lymphatic system: rarely - hemorrhagic anemia, hemorrhagic diathesis, spontaneous occurrence of hematomas.

From the nervous system: rarely - cranial hemorrhages, hemorrhagic stroke.

Special senses: infrequently - conjunctival hemorrhage; rarely - hemorrhages in the tissue of the eyeball, hemorrhages in the retina, sclera, vitreous.

On the part of the hearing: rarely, ear bleeding.

Cardiovascular: often - hematomas; rarely - pericardial bleeding, other types of bleeding, bleeding into the abdominal cavity, hemorrhagic shock.

Respiratory: often - nosebleeds; infrequently - hemoptysis; rarely, pulmonary alveolar bleeding.

From the digestive 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 mouth, abdominal wall hematomas, Malory-Weiss syndrome, gastric bleeding, bleeding in the small intestine.

From the skin: infrequently - bruising, bleeding from the skin; rarely - petechiae, purpura, increased tendency to bleeding, callus, bleeding from skin ulcers.

Musculoskeletal system: rarely - hemorrhage in the muscles.

Urogenital: often - hematuria; rarely, urinary system bleeding.

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 menopause.

Reactions at the injection site and other reactions: infrequently - hematoma at the injection site, hematoma at the puncture site of the vessel, bleeding from a wound, traumatic hematoma; seldom - 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.

Laboratory values: infrequently - the presence of 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.

Contraindications Eliquis

- 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 hypertension;

- severe abnormal liver function, liver disease, accompanied by disorders in the blood coagulation system and a clinically significant risk of bleeding;

- impaired renal function with a CC of less than 15 ml / min, as well as use in patients on dialysis;

- simultaneous application of drugs, the effect of which may be associated with the development of serious bleeding, such as any anticoagulant drugs, unfractionated Heparin , low molecular weight heparins (enoxaparin, dalteparin), derivatives of heparin (fondaparinux), oral anticoagulants (warfarin, rivaroxaban, dabigatran), for with the exception of those situations when the patient is transferred to therapy or with therapy with apixaban or if unfractionated heparin is prescribed in doses necessary to maintain the patency of the patient central venous 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);

- children and adolescents under 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.

Carefully

Experience with the use of Eliquis with thrombolytic agents for the relief of acute ischemic stroke is limited.

Apixaban should be used with caution in patients with moderate to mild hepatic impairment (grades A or B according to the Child-Pugh classification).

Apixaban should be used with caution 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 (in particular, Ketoconazole , iraconazole, taconic antifungal agents (eg, ketoconazole, iconacozelemide, P-glycoprotein), such as azole antifungal agents (in particular, ketoconazole, iconaconol, Isoconazole, Io-antifungal agents (eg, ketoconazole, iconaconol, Iponic anti-fungal medication), such as azole antifungal agents (eg, ketoconazole, iconacozol, Ioaconazole, Io-antifungal agents) ), HIV protease inhibitors (eg, ritonavir). You should also be careful when using apixaban with powerful inducers of CYP3A4 isoenzyme and P-glycoprotein (in particular, rifampicin, phenytoin, Carbamazepine , phenobarbital or Hypericum perforatum preparations).

It is not recommended to use the drug Eliquis in liver diseases, accompanied by abnormalities in the blood coagulation system and a clinically significant risk of bleeding. It is necessary to stop using Eliquis when heavy bleeding occurs.

If a complication in the form of bleeding occurs, therapy with Eliquis 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 can be considered in life-threatening conditions that cannot be controlled using the above methods,The possibility of introducing recombinant coagulation factor VIIa may be considered, although there is currently no experience with this coagulation factor in patients receiving apixaban therapy.

Caution should be exercised when using apixaban with NSAIDs (including acetylsalicylic acid), due to the fact that these drugs increase the risk of bleeding.

As part of a clinical trial of Eliquis^® not used in patients undergoing emergency surgery for a hip fracture, so its effectiveness and safety in this category of patients has not been studied.

Use during pregnancy and breastfeeding Eliquis

Use during pregnancy

During preclinical studies, no toxicity of the drug Eliquis in relation to reproductive function was detected. There is limited information about the use of the drug Eliquis^® during pregnancy. The use of apixaban during pregnancy is not recommended.

Use during breastfeeding

In rat studies, the concentration of Eliquis in breast milk was many times higher than that in blood plasma (C_max about 8 times higher, AUC about 30 times higher), which may indicate an active transport of the drug into 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 necessary, use of the drug Eliquis^® during lactation, breastfeeding should be discontinued.

Impact on fertility

Apixaban did not affect fertility in animal studies.

Use for violations of liver function Eliquis

Caution should be exercised when taking the drug Eliquis in patients with mild to moderate hepatic insufficiency (class A or B on Child-Pugh), while dose adjustment is not required. The use of Eliquis in patients with severe liver failure is not recommended.

Application for violations of renal function Eliquis

In patients with impaired mild, moderate or severe kidney function with a decrease in CC to 15 ml / min, no dose adjustment is required. Data on the use of the drug in patients with QA <15 ml / min, as well as in patients on dialysis, are not available. The use of the drug Eliquis in this category of patients is not recommended

Use in children

Contraindicated in children under 18 years old

Use in elderly patients

Dose adjustment of the drug in elderly patients is not required.

special instructions

Risk of bleeding

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.^®.

Elikvis^® not recommended for patients with liver disease, accompanied by abnormalities in the blood clotting system and a clinically significant risk of bleeding.

In high-risk patients after acute coronary syndrome, with the presence of multiple cardiac and non-cardiac concomitant diseases, a significant increase in the risk of bleeding was shown 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 cancel.

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 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.

Surgical intervention associated with a hip fracture

As part of a clinical trial of 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 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.^®. 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 half-life) between the last dose of apixaban and the catheter removal should be observed, so at least one dose of apixaban should be missed before catheter removal.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.

Patients with artificial heart valves

The safety and efficacy of the drug in patients with artificial heart valves with atrial fibrillation and without it has not been studied. Use of the drug Eliquis^® for this group of patients is not recommended.

Treatment of deep vein thrombosis and pulmonary embolism

It is not recommended to replace therapy with unfractionated heparin by Eliquis.^® in the period of initiation of treatment of patients with pulmonary embolism with unstable hemodynamics, the possible holding of thrombolysis or pulmonary artery thrombectomy.

Influence on ability to drive motor transport and control mechanisms

Elikvis^® does not have a significant impact on the ability to drive vehicles and work with mechanisms.

Overdose of Eliquis

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 overdose of this drug, you can consider the use of Activated carbon . 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 (C_max did not change). T_1/2 apixaban decreased from 13.4 to 5.3 and 4.9 h, respectively.

Antidote not known. It is not expected that the use of hemodialysis in overdose of apixaban will be an effective measure.

Drug Interactions Eliquis

Effect of other drugs on apixaban pharmacokinetics

Inhibitors of the isoenzyme CYP3A4 and P-glycoprotein

The combination of apixaban with ketoconazole (at a dose of 400 mg, 1 time / day), which is a potent inhibitor of both the CYP3A4 isoenzyme and P-glycoprotein, resulted in a 2-fold increase in the mean AUC value of apixaban and C_max - 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.

Preparations not related to the potent inhibitors of the 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 / day, led to an increase in mean AUC values ​​of apixaban 1.4 times and average C values_max - 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 average values ​​of AUC and C_max apixaban 1.5 and 1.6 times, respectively. At the same time, there was an increase in the values ​​of the blood coagulation system parameters (prothrombin time, INR and APTT). However, no effect of naproxen on platelet aggregation induced by arachidonic acid and clinically significant lengthening of the bleeding time was observed.

Do not adjust the dose of apixaban when combined with moderate inhibitors of the isoenzyme CYP3A4 and / or P-glycoprotein.

Inductors of isoenzyme CYP3A4 and P-glycoprotein

The combination of apixaban with rifampicin (a powerful inducer of CYP3A4 isoenzyme and P-glycoprotein) resulted in a decrease in the average values ​​of AUC and C_max 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.

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 agents 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.

Despite the results obtained in healthy volunteers, some sensitive patients may have a more pronounced pharmacokinetic interaction between apixaban and platelet aggregation inhibitors.

Combining apixaban with clopidogrel (75 mg 1 time / day) or a combination of clopidogrel (75 mg) and acetylsalicylic acid (162 mg 1 time / day) or prasugrel (60 mg followed by a dose of 10 mg 1 time / day) in phase I a clinical study did not lead to an increase in bleeding time or a more pronounced inhibition of platelet aggregation compared with the use of these antiplatelet agents in monotherapy.Increased blood coagulation system (prothrombin time, MHO and APTT) were consistent with 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 inhibitors of thrombin II (eg, desirudin), thrombolytic drugs, receptor antagonists to glycoproteins IIb / IIIa, Dipyridamole , dextran, sulfinpyrazon, en