Eliquis pills 5mg, 20pcs

Composition

1 tablet contains apixaban 5 mg. excipients: lactose-100.5 mg; MCC-82 mg; croscarmellose sodium-8 mg; sodium lauryl sulfate-2 mg; magnesium stearate-2.5 mg film shell: Opadry II yellow / pink (hypromellose 15 cps-2.96 mg, lactose monohydrate-2.48 mg, titanium dioxide-1.87 mg, triacetin-0.64 mg, iron oxide red dye-0.046 mg) – 8 mg

Pharmacological action

Direct-acting anticoagulant – selective inhibitor of blood coagulation factor Xa.

The mechanism of action of apixaban is to inhibit the activity of FXa. As a result, apixaban changes the values of blood clotting system parameters: it extends prothrombin time, MHO, and activated partial thromboplastin time (APTT). Changes in these parameters when using the drug in a therapeutic dose are insignificant and individual. Therefore, their use for the purpose of evaluating the pharmacodynamic activity of apixaban is not recommended.

Apixaban inhibition of FXa activity was demonstrated 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 activity values are observed when the cmaxof apixaban in blood plasma is reached.

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 the dose and concentration of apixaban are more pronounced and less variable than blood clotting parameters.

The expected maximum and minimum anti-FXa activity of apixaban at steady state, when used at a dose of 2.5 mg 2 times / day, is 1. ZME/ml (5/95 percentiles-0.67 IU / ml-2.4 IU / ml) and 0.84 IU/ml (5/95 percentiles -0.37 IU/ml – 1.8 IU/ml), respectively, which correlates with fluctuations in this indicator in the interval between doses of the drug (less than 1.6 times).

While apixaban therapy does not require routine monitoring of its plasma concentration, however, performing the Rotachrom anti-FXa reactivity test may be useful for deciding whether to continue therapy.

Indications

• prevention of venous thromboembolism in patients after elective hip or knee replacement;
• prevention of strokes, systemic thromboembolism and reduction of mortality in patients with atrial fibrillation. The exception is patients with severe to moderate mitral stenosis or artificial heart valves.

Contraindications

• hypersensitivity to any component of the drug;
• clinically significant bleeding;
• severe hepatic
• impairment; impaired renal function with a creatinine clearance of less than 15 ml / min, as well as use in patients on dialysis;
• pregnancy;
• breastfeeding;
• age up to 18 years.
• It is not recommended to simultaneously use apixaban with drugs that may be associated with the development of serious bleeding.

With caution:  apixaban should be used with caution in patients with moderate to mild hepatic impairment (Child-Pugh class A or B); during spinal/epidural anesthesia or spinal/epidural puncture (see “Special Instructions”); in patients receiving systemic therapy with potent inhibitors of the CYP3A4 isoenzyme and P-glycoprotein, such as azole antifungal agents (in particular ketoconazole, itraconazole, voriconazole and posaconazole), HIV protease inhibitors (for example, ritonavir); when using apixaban with powerful inducers of the CYP3A4 isoenzyme and P-glycoprotein (in particular, rifampicin, phenytoin, carbamazepine, phenobarbital or St. John’s wort preparations).

Side effects

The frequency of adverse reactions is defined as: often – ≥1/100,

Prevention of venous thromboembolism in patients after elective hip or knee replacement surgery

Adverse reactions were reported in 11% of patients treated with apixaban 2.5 mg twice daily. As with other anticoagulants, bleeding may occur in patients with risk factors such as organic lesions that may be accompanied by bleeding. The most common side effects were anemia, bleeding, bruising, and nausea. The adverse reactions that developed in patients undergoing orthopedic surgery during apixaban therapy are presented below.

Blood and lymphatic system disorders:  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 a decrease in the number of platelets).

From the immune system:  rarely — hypersensitivity.

From the side of the visual organ:  rarely — hemorrhages in the eyeball tissue (including conjunctival hemorrhage).

From the CCC side:  infrequently-arterial hypotension (including hypotension during the procedure).

Respiratory system disorders:  infrequently-nosebleeds; rarely-hemoptysis.

From the gastrointestinal tract:  often — nausea; infrequently-gastrointestinal bleeding (including vomiting with an admixture of blood and melena), the presence of unchanged blood in the feces; rarely-rectal bleeding, bleeding from the gums.

Liver and biliary tract disorders:  infrequently — increased transaminase activity, including increased ALT, AST, GGTP activity, pathological changes in liver function tests, increased ALP activity in the blood, increased bilirubin concentration in the blood.

From the musculoskeletal system:  rarely-muscle hemorrhage.

From the urinary system:  infrequently — hematuria (including corresponding changes in the results of laboratory tests).

Other services:  often-closed trauma; infrequently-hemorrhage 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 site of catheter insertion), the presence of discharge from the wound, hemorrhage in the incision area (including hematoma in the incision area), bleeding during surgery.

Prevention of strokes and systemic embolism in patients with atrial fibrillation

From the immune system:  infrequently — hypersensitivity (including drug-induced hypersensitivity reactions, such as skin rash and anaphylactic reactions, allergic edema).

Nervous system disorders:  infrequently — intracranial hemorrhages, subarachnoid hemorrhages, subdural hematomas, hemorrhages in the spinal canal, spinal hematoma.

From the side of the visual organ:  often — hemorrhages in the eyeball tissue (including conjunctival hemorrhage).

From the CCC side:  often — other types of bleeding, hematomas; infrequently-bleeding in the abdominal cavity.

Respiratory system disorders:  often-nosebleeds; infrequently-hemoptysis; rarely-bleeding in the respiratory system (including pulmonary alveolar bleeding, laryngeal and pharyngeal bleeding).

From the gastrointestinal tract:  often — gastrointestinal bleeding (including vomiting with an admixture of blood and melena), rectal bleeding, bleeding from the gums; infrequently-hemorrhoidal bleeding, the presence of unchanged blood in the feces, bleeding into the oral cavity; rarely-retroperitoneal hemorrhage.

From the urinary system:  often — hematuria.

From the side of the reproductive system:  infrequently — intermenstrual vaginal bleeding, urogenital bleeding.

Injection site reactions:  infrequently – bleeding at the injection site.

Laboratory parameters:  infrequently — a positive reaction when analyzing feces for hidden blood.

Other services:  often-closed trauma; infrequently-traumatic bleeding, bleeding after the procedure, hemorrhage in the incision area.

Interaction

Effect of other drugs on the pharmacokinetics of apixaban

Inhibitors of CYP3A4 and P-glycoprotein. The combination of apixaban with ketoconazole (at a dose of 400 mg, once a day), which is a powerful inhibitor of both the CYP3A4 isoenzyme and P-glycoprotein, led to an increase in the average apixaban AUC by 2 times and_{the average cmax by} 1.6 times. Dose adjustment of apixaban in 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 that are not considered to be potent inhibitors of the CYP3A4 and P-glycoprotein isoenzyme (for example, diltiazem, naproxen, amiodarone, verapamil, quinidine) are likely to increase the concentration of apixaban in blood plasma to a lesser extent. For example, diltiazem (a moderate inhibitor of the CYP3A4 isoenzyme and a weak inhibitor of P-glycoprotein) at a dose of 360 mg 1 time per day, led to an increase in the average AUC of apixaban by 1.4 times and the average values of_cmax — by 1.3 times. Naproxen (a P-glycoprotein inhibitor), when administered at a dose of 500 mg in healthy volunteers, caused an increase in the average values of AUC and_cmax apixaban increased 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, INR, and APTT). However, there was no effect of naproxen on arachidonic acid-induced platelet aggregation, as well as a clinically significant prolongation of bleeding time.

Dose adjustment of apixaban in combination with moderate inhibitors of the CYP3A4 isoenzyme and / or P-glycoprotein is not required.

Inducers of the CYP3A4 isoenzyme and P-glycoprotein. The combination of apixaban with rifampicin (a potent inducer of the CYP3A4 isoenzyme and P-glycoprotein) resulted in a decrease in the average apixaban AUC and cmax values 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 St. John’s wort preparations) can also lead to a decrease in the concentration of apixaban in blood plasma. Dose adjustment of apixaban is not required when it is combined with drugs of this group, but these drugs should be combined with caution.

Anticoagulants, platelet aggregation inhibitors, and NSAIDs. After co-use 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.

There were no signs of pharmacokinetic or pharmacodynamic interaction of apixaban with acetylsalicylic acid (at a dose of 325 mg,1 time per day) in healthy people.

The combination of apixaban with clopidogrel (75 mg, once daily) or a combination of clopidogrel (75 mg) and acetylsalicylic acid (162 mg, once daily) in a phase I clinical study did not lead to an increase in bleeding time or further inhibition of platelet aggregation compared to the use of these antiplatelet agents in monotherapy. The increase in blood clotting parameters (PV, INR, and APTT) was consistent with the effects of apixaban alone.

It is not recommended to use concomitantly drugs that may be associated with the development of serious bleeding, such as unfractionated heparin or heparin derivatives (including low-molecular-weight heparins), FXa-inhibiting oligosaccharides (e. g. fondaparinux), direct thrombin II inhibitors (e. g. 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 can be used in doses necessary to support the patency of the central venous or arterial catheter.

In patients after elective hip or knee replacement surgery, co-use of apixaban with other antiplatelet agents or antithrombotic drugs is not recommended.

Combination with other medications. There was no clinically significant pharmacokinetic or pharmacodynamic interaction between apixaban and atenolol or famotidine.

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, but it was accompanied by a decrease in the average AUC and_cmax values of apixaban by 15 and 18%, respectively, compared with the monotherapy regimen. use of apixaban (10 mg) with famotidine (40 mg) had no effect on apixaban AUC or_{cmax values}.

Effect of apixaban on the pharmacokinetics of other drugs

In studies in vitro apixaban not inhibited the activity of the isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (inhibitory concentration (IC50) >45 µmol/l) and at the same time weakly inhibited the activity of isoenzyme CYP2C19 (IC50 >20 µmol/l) in concentrations much higher than the C_max of the drug in the blood plasma in its clinical application. Apixaban is not an inducer of CYP1A2, CYP2B6, or CYP3A4/5 isoenzymes at concentrations up to 20 mmol/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 P-glycoprotein activity. In studies in healthy volunteers, apixaban did not significantly alter the pharmacokinetics of digoxin, naproxen, or atenolol.

How to take, course of use and dosage

Inside, regardless of food intake.

In case of missed admission, the drug should be taken as soon as possible, and then continue taking it 2 times a day in accordance with the original scheme.

In patients after elective hip or knee replacement surgery: 2.5 mg 2 times a day (the first dose 12-24 hours after surgery).

In patients who have undergone hip replacement, the recommended duration of therapy is 32-38 days, for the knee joint-10-14 days.

In patients with atrial fibrillation: 1 tablet of 5 mg 2 times a day.

Special patient groups

1. Patients with atrial fibrillation in combination 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 mmol / L) – the recommended dose of Eliquis is reduced to 1 table 2.5 mg 2 times a day.

2. Patients with impaired renal function. In patients with mild, moderate or severe renal impairment with a decrease in creatinine clearance of up to 15 ml / min, no dose adjustment of apixaban is required (with the exception of the patients indicated in paragraph 1). In patients with severe renal impairment with a creatinine clearance of 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 Eliquis in patients with mild to moderate hepatic insufficiency (Child-Pugh Class A or B), and no dose adjustment is required. The use of the drug in patients with severe hepatic insufficiency is not recommended.

4. Elderly patients. Dose adjustment of the drug in elderly patients is not required (except for the patients indicated in clause 1).

5. Body weight. Dose adjustment depending on the patient’s body weight is not required (except for the patients listed in clause 1).

6. Gender. No dose adjustment is required depending on the patient’s gender.

7. Race and ethnic origin. No dose adjustment is required depending on the patient’s race or ethnic origin.

Switching from or to parenteral anticoagulant therapy

Switching from parenteral anticoagulants to Eliquis and vice versa can be performed at the time of the next scheduled intake of the drug to be canceled (the next dose of the drug to be canceled is not taken).

Switching from or to warfarin or other vitamin K antagonists

Transfer of patients from warfarin or other vitamin K antagonists to Eliquis® therapy should be performed if the patient’s INR is below 2.

When transferring patients from Eliquis®therapy for warfarin or other vitamin K antagonists, Eliquis therapy should be continued for 48 hours after the first dose of warfarin or other vitamin K antagonists

. Surgical and invasive procedures

Eliquis should be discontinued 2-3 days before elective surgery or an invasive procedure. If it is not possible to postpone the procedure, special care should be taken, given the increased risk of bleeding. It is also necessary to assess the ratio of the risks of bleeding and delaying the operation.

Overdose

Symptoms: the risk of bleeding increases. In controlled clinical trials, apixaban was administered orally to 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 a day for 3 days); no clinically significant adverse effects were observed.

Treatment: The use of activated carbon may be considered. The antidote of the drug is unknown.

Special instructions

In patients with atrial fibrillation and conditions requiring the use of monotherapy or therapy with a combination of two antiplatelet drugs, the benefit/risk ratio should be carefully evaluated before starting concomitant use with Eliquis.

Eliquis is not recommended for use in patients with liver disease associated with disorders in the blood coagulation system and a clinically significant risk of bleeding.

It has been shown that high-risk patients after acute coronary syndrome, with multiple cardiac and non-cardiac comorbidities, experienced a significant increase in the risk of bleeding when apixaban and acetylsalicylic acid were co-administered or a combination of acetylsalicylic acid and clopidogrel compared to placebo.

As with other anticoagulants, patients taking Eliquis should be closely monitored for the development of bleeding. If severe bleeding occurs, Eliquis should be discontinued.

If hemorrhagic complications develop, it is necessary to cancel treatment with the drug and perform an examination to identify the source of bleeding.If necessary, appropriate treatment is prescribed, in particular surgical stopping of bleeding or transfusion of freshly frozen blood plasma.

Discontinuation of anticoagulant therapy, including apixaban, with active bleeding before elective surgery or an invasive procedure may lead to an increased risk of thrombosis. Long-term discontinuation of therapy should be avoided and, if apixaban therapy needs to be temporarily discontinued, 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, can cause persistent or irreversible paralysis. This risk may increase even more 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 before the first dose of Eliquis is administered. A similar increase in risk may occur when performing traumatic or multiple punctures of the epidural or subarachnoid spaces. Patients should be frequently monitored for signs of nervous system dysfunction (in particular, numbness or weakness of the lower extremities, impaired bowel or bladder function).

With the development of such disorders, it is necessary to perform an emergency examination and treatment. Before performing surgery on the epidural or subarachnoid spaces in patients receiving anticoagulants, including for the prevention of thrombosis, it is necessary to assess the ratio of potential benefits and risks.

Influence on the ability to drive vehicles and work with other mechanisms. Eliquis does not significantly affect the ability to drive a car and work with mechanisms.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Apixaban

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Prevention of heart attacks and strokes, Prevention of thrombosis