Eliquis 5mg pills №20

Indications

- prevention of venous thromboembolism in patients after planned hip or knee arthroplasty;

- prevention of strokes, systemic thromboembolism and reduction of mortality in patients with atrial fibrillation. The exceptions are patients with severe and moderate mitral stenosis or with artificial heart valves.

Dosage and administration

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).

Have patients undergoing hip arthroplastyThe recommended duration of treatment is 32 to 38 days, knee joint - from 10 to 14 days.

Atrial fibrillation patients prescribe 5 mg 2 times / day.

Use in special patient groups

1. Do atrial fibrillation patients in combination with two or more of the following characteristics - age older than 80 years, body weight less than 60 kg or plasma creatinine concentration ≥1.5 mg / dl (133 μmol / l) recommended dose of Eliquis^® reduced to 2.5 mg 2 times / day.

2. When renal dysfunction mild to moderate to severe QC up to 15 ml / min dose adjustment of apixaban is not required (with the exception of patients referred to in paragraph 1).

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.

3. Care should be taken when taking Eliquis^® patients with mild and moderate hepatic insufficiency (class A or B according to Child-Pugh classification), while dose adjustment is not required.

Use of the drug in patients with severe liver failure Not recommended.

4. Correction of the drug dose in elderly patients not required (with the exception of patients referred to in paragraph 1).

5. Dose adjustment depending on body mass the patient is not required (with the exception of patients referred to in paragraph 1)

6Dose adjustment of the drug depending on the floor no patient required.

7. Dose adjustment of the drug 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to Eliquis^® and vice versa, it can be performed at the time of the next scheduled intake of the drug being withdrawn (with the next dose of the drug being withdrawn not being taken).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.

Surgical and invasive procedures

Elikvis^® should be canceled 2-3 days before the 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 risk of bleeding and the delay in the operation.

Side effect

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 the results of laboratory tests), bleeding (includinghematoma, 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 incision area (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.

Contraindications

- hypersensitivity to any component of the drug;

- clinically significant bleeding;

- severe abnormal liver function;

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

- pregnancy;

- breast-feeding;

- children's and teenage 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.

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

Apixaban should be used with caution when performing spinal, epidural anesthesia or 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, morphonazole and plasmone). HIV (for example, 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).

The drug is recommended to be used with caution in conditions characterized by an increased risk of bleeding: congenital or acquired bleeding disorders; with acute gastrointestinal ulcers; bacterial endocarditis; thrombocytopenia; thrombocytopathy; a hemorrhagic stroke in the anamnesis; recent surgery on the brain or spinal cord, as well as on the organ of vision; with severe uncontrolled hypertension.

In addition, caution should be exercised while 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 lactation

There is only limited information on the use of the drug 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, use of the drug Eliquis^® during lactation, breastfeeding should be discontinued.

Application for violations of the liver

Care should be taken when taking Eliquis patients with mild to moderate hepatic insufficiency (class A or B on Child-Pugh), no dose adjustment is required. Use of the drug in patients with severe liver failure Not recommended.

Application for violations of kidney function

Have patients with impaired mild, moderate or severe kidney function with a decrease in CC to 15 ml / min dose adjustment of the drug is not required. Data on the use of the drug in patients with QA <15 ml / min, as well as in patients on dialysisare missing. 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

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.

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 is required regarding the development of manifestations of impaired function of the nervous system (in particular, numbness or weakness of the lower limbs, impaired function of the intestine or bladder). 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 motor transport and control mechanisms

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

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 overdose of this drug, you can consider the use of Activated carbon . Antidote not known.

Drug interaction

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 associated with impaired arachidonic acid metabolism and a 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 powerful inducers of the CYP3A4 isoenzyme and P-glycoprotein (in particular, phenytoin, carbamazepine, phenobarbital, or Hypericum perforatum) can also lead to a decrease in the concentration of apixaban in the blood plasma. It is not necessary to adjust the dose of apixaban when it is combined with the means of this group, but it is necessary to combine these means 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 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.

Combining apixaban with clopidogrel (75 mg 1 time / day) or a combination of clopidogrel (75 mg) and acetylsalicylic acid (162 mg 1 time / day) in the first phase of a clinical study did not lead to an increase in bleeding time or further inhibition of platelet aggregation compared to 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, sulfinpyrazone, 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 planned hip or knee arthroplasty, co-administration of apixaban with other antiplatelet agents or other 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 average AUC and C values_max apixaban by 15% and 18%, respectively, compared with the monotherapy regimen. Administration of apixaban (at a dose of 10 mg) with famotidine (at a dose of 40 mg) did not affect the AUC or C values._max apixabana

The effect of apixaban on the pharmacokinetics of other drugs

In in vitro studies, apixaban did not inhibit the activity of isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (inhibitory concentration (IC₅₀)> 45 µmol / l), however, a slight inhibition of the activity of the CYP2C19 isoenzyme (IC₅₀ > 20 μmol / l) apixaban at a concentration significantly higher than C_max drug in plasma at 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.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not higher than 30 ° C.