Eliquis 5mg Pfizer prevents the events of venous thrombolytic embolization, stroke (20 tablets)

Dosage form Box of 2 blisters x 10 tablets
Specifications Apixaban

Ingredient

Composition information	Content
Apixaban	5mg

Uses

indications

Eliquis drug indicated in the following cases:

Prevention of venous thrombosis events (VTE Thromboembolic Events (VTE) in adult patients undergo surgery to replace hip or knee joints according to the program. (Tia); age> 75; Hypertension, diabetes, symptomatic heart failure (2 degrees II according to the classification of the New York Heart Association - NYHA). Far.

Active mechanism

Apixaban is a strong, oral inhibitor inhibitor, inhibited and has a high selective selection of the location of the remote factor. Apixaban does not require antithrombin III to have anticoagulant effects. Apixaban inhibits the distant factor and remote factors that have thrombosis and activity of prothrombinase. Apixaban does not work directly on platelet gathering but indirectly inhibits platelet aggregation output by thrombin.

By inhibiting the remote factor, Apixaban prevents the formation of thrombin and blood clots. Apixaban's preclinical studies on animal models have proved that Apixaban effectively prevented blood clotting in preventing thrombosis in the arteries and veins at doses that still maintain hemostasis.

The impact of learning

The impact of Apixaban's learning reflects its mechanism of action (inhibitors of factors).

As a result of the inhibition of remote factors, Apixaban extends the time in blood clotting tests such as prothrombin time (prothrombin time - pt), INR and the time of thromboplastin activated (Activated Partial Thromboplastin Time

Do not use these changes to assess the impact of apixaban. In the production of thrombin production, apixaban reduced endogenous thrombin, a measure of plasma thrombin production in humans.

Apixaban also shows distant factor activity, as evidenced by a decrease in enzyme activity in many distant commercial commercial kits, but the result between kit is different. Only data from clinical trials allows quantitative heparin rotachrom color ".

Airal factor activity has a close linear correlation with an apixaban concentration in plasma, reaching maximum value at the time of apixaban concentration in plasma peaks. The correlation between apixaban concentration in plasma and distant activity is almost linearly on a wide range of the apixaban dose.

In patients with apixaban, preventing venous thrombolytic embolism after hip or knee joint replacement surgery, the results show that the level of fluctuations from the top to here is less than 1.6 times. In patients with atrial fibrillation due to non -valve disease using apixaban to prevent stroke and systemic embolism, the results show that the level of fluctuations from the decision here is less than 1.7 times. In patients using apixaban to treat deep vein thrombosis and pulmonary embolism or prevent recurrence of deep veins and pulmonary embolism, the results show that the level of fluctuations from the top to the bottom is less than 2.2 times.

* The target group is adjusted to the dose based on the criteria of 2 of 3 data in the Aristotle study.

Although the treatment with apixapan does not require regular monitoring of blood concentrations in the blood, testing for remote factors that are effective in special cases when knowing the concentration of apixaban in the blood can support clinical decisions, such as overdose and emergency surgery.

Clinical efficiency and safety

Prevention of venous thrombosis (VTEP): Surgery to replace hip or knee joints according to the program.

Apixaban's clinical trial program is designed to prove the effectiveness and safety of apixaban in preventing venous thrombolytic embolism on many adult patients through hip or knee joint replacement surgery according to the program.

Total 8,464 patients are randomly distributed in two key, double blind, multinational studies that compare 2.5 mg apixaban apixaban twice (4,236 patients) or Enoxaparin 40 mg once a day (4,228 patients). Including this total of 1,262 patients (618 in the apixaban group) aged 75 and older, 1,004 patients (499 in the apixaban group) have low body weight ( ADVANCE-3 research includes 5,407 patients who are replaced with groin joints under the program, and the ADVANCE-2 research includes 3,057 patients who are replaced by knee joints.

Objects use 2.5 mg apixaban by oral 2 times (PO BID) or Enoxaparin 40 mg injected once a day (SC OD).

The first apixa dose was used for 12 to 24 hours after surgery, while Enoxaparin was started for 9 to 15 hours before surgery. Both Apixaban and Enoxaparin are used for 32-38 days in the ADVANCE-3 study and for 10-14 days in the ADVANC-2 study.

Based on the patient's history in the research groups of Advance-3 and Advance-2 (8,464 patients), 46% of hypertension, 10% have hyperlipidemia, 9% of diabetes, and 8% of coronary artery disease.

Apixaban shows that there is a statistical outstanding decrease in the evaluation criteria is the combined criterion of all deaths of venous thromboembolism due to all causes, and in the criteria for evaluating the serious venous thrombosis is a complex criterion of deep vein thrombosis, pulmonary coronary embarrassment, and deaths related to intravenous venous embolization, compound of energy in replacement pulse in the pulp in the surgery in the surgery instead of the joint surgery in the joint surgery in the joint surgery in the joint surgery in the joint surgery or knee joint according to the program (see Table 4).

Criteria for assessment of safety for serious bleeding, a complex criterion of serious bleeding and non -serious bleeding with clinical significance (CRNICALLANG NGAJOR (CRNM), and all types of bleeding shows the same ratio in patients treated with 2.5 mg apixaban apixaban compared to Enoxaparin 40 mg (see table 5). All types of hemorrhage include hemorrhage at the surgical position.

The overall ratio of unwanted effects of hemorrhage, anemia and abnormal transaminase (for example, ALT concentration) has a lower value in patients using apixaban compared to Enoxaparin in phase II and phase III studies in the replacement of groin or knee joints according to the program.

In the study of knee replacement surgery during the expected treatment period, in the apixaban branch diagnosed 4 cases of pulmonary embolism compared to no cases of pulmonary embolism in Enoxaparin branch. There is no explanation for this higher number of pulmonary embolism.

Prevention of rules and systemic embolism in patients with atrial fibrillation due to valve disease (NVAF).

A total of 23,799 patients who are randomly selected in the clinical program (Aristotle: Apixaban compared to Warfarin, Averroes: Apixaban compared to Aspirin) include 11,927 randomly distributed by APixaban.

The program is designed to prove the effectiveness and safety of apixaban to prevent stroke and body embolism in patients with atrial fibrillation due to valve disease (NVAF) and have one or more additional risk factors, such as:

Before that had a stroke or transient ischemic anemia (ray).

age> 75.

Hypertension.

In the Aristotle study, a total of 18,200 patients were randomly selected for double blindness treatment with 5 mg apixaban twice (or 2.5 mg twice a day in selected patients [4.7%]) or Warfarin (about Inr target 2.0-3.0), the patient was given medication for an average of 20 months. The average age is 69.1 years, the score is 2.1 and 18.9% of patients with stroke or previous rays.

In the study, Apixaban achieved a clear superiority in terms of statistical in the main evaluation criteria for stroke prevention (hemorrhage or ischemia) and systemic embolism (see Table 6) compared to Warfarin.

For patients who are randomly selected to use warfarin, the average percentage of time within the therapy (TTR) (INR 2-3) is 66%.

Apixaban shows a decrease in stroke and clogged frame compared to Warfarin through different levels of TTR centers, in the highest self -separation point of TTR by the center, the risk rate for apixaban compared to Warfarin is 0.73 (CI 95%, 0.38;

The important auxiliary evaluation criterion is serious bleeding and death due to all causes tested with a predetermined test strategy to control the type 1 error (Type 1 Error) overall in the test.

The statistical obvious superiority is also achieved in the important assessment criteria of both serious bleeding and death due to all causes (see Table 7). When Inr is better monitored, Apixaban has shown that it is more beneficial than Warfarin because of reducing the mortality rate for all causes.

Overall drug suspension rate due to unwanted effects is 1.8% for apixaban and 2.6% for warfarin in Aristotle research.

The results of the effectiveness of the divisions are predefined, including ChADS points), age, body weight, gender, kidney function, stroke or previous rays and diabetes are consistent with the main results of the effectiveness of the entire research group in the test.

Serious gastrointestinal bleeding ratio (including upper digestive tract, lower gastrointestinal tract, and rectal bleeding) is 0.76%/year for apixaban and 0.86%/year for warfarin.

The results of serious bleeding for previous subgroups, including Chads2 points, age, body weight, gender, kidney function, stroke or previous rays and diabetes are consistent with the results for the entire research group
in testing.

Averroes research

In Averues research, a total of 5,598 patients are considered by the researchers to be unsuitable for vitamin K anti -vitamin K drugs that are randomly selected for treatment with an apixaban 5 mg twice a day (or 2.5 mg of bongs in patients selected [6.4%]) or aspirin.

Aspirin is used once a day with a dose of 81 mg (64%), 162 (26.9%), 243 (2.1%), or 324 mg (6.6%) as decided by the researcher.

Patients were given drugs for 14 months on average. The average age is 69.9 years, the average Chads2 score is 2.0 and 13.6% of patients with mutant or previous rays.

The reason is not suitable for vitamin K anti -vitamin K drugs in Averroes research, it is impossible/likely not to achieve the Inr values within the required range (42.6%), the patient refuses to treat with vitamin K anti -vitamin (37.4%), ChADS2 points = 1 and the doctor does not recommend the use of anti -vitamin K (21.3%), does not believe that the patient will comply with the anti -vitamin K (15.0) instructions for 15.0%) Towels/difficulties are predicted to meet when contacting patients in case of emergency dose changes (11.7%).

Averroes is stopped before the proposal of the independent data monitoring committee due to the clear evidence of the sudden decline in the body and the body and safety properties that meet the requirements of the reagent.

The overall stop rate of unwanted touch measurement is 1.5% for apixaban and 1.3% for aspirin in Averroes research.

In the study, Apixaban achieved a clear superiority of statistics in the main evaluation criteria for sudden prevention (due to hemorrhage and local blood burning) and systemic embolism (see Table 8) compared to aspirin.

There is no significant difference in statistics in the serious bleeding ratio between apixaban and aspirin (see Table 9).

Deep venous thrombosis (DVT), pulmonary embolism (PE) and prevention of recurrence DVT and PE (VTET}

Clinical testing program (Amplify: Apixaban compared to Enoxaparinuwarfarin, Amplify-Wide Amplify-Research: Apixaban compared to Placebo) Designed to prove the safety and effectiveness of apixaban in the treatment of deep veins and pulmonary veins (amplifying amplify) and expansion therapy to prevent reducing blood tumors and in-depth therapy to prevent relapse. Pulmonary vessels after 6 to 12 months of anticoagulant treatment for deep vein thrombosis and/or coordinated embolism (Wide ampliey-research).

Both studies are random tests, parallel groups, double blindness, multinational countries in patients with deep vein thrombosis with symptoms and/or symptomatic pulmonary embolism. All criteria for safety and effectiveness are assessed by an independent blind council.

Amplify research

In the study of a total of 5,395 amplify patients who are randomly selected for treatment with an apixaban 10 mg twice a day oral for 7 days, followed by an apixaban 5 mg twice a day by oral for 6 months, or Enoxaparin 1 mg/kg twice a day injected under the skin for at least 5 days (until INR≥ 2) and Warfarin (about INR target 2,0-3,0) by drinking in 6 drinks in 6 or drink month.

The average age is 56.9 and 89.8% of patients who are randomly selected to have an unconstantic thrombolytic embolism.

For patients who are randomly recruited to use warfarin, the average percentage of time within the therapy (INR 2.0-3.0) is 60.9. Apixaban shows a decrease in venous hemocystic events with symptoms of relapse or death associated with venous thromboembolism events through different levels of TTR centers; In the highest quartet of TTR according to the center, the relative risk of apixaban compared to Enoxaparin/Warfarin is 0.79 (CI 95%, 0.39; 1,61).

In the study, Apixaban shows that it is not inferior to Enoxaparin/Warfarin in the main evaluation criteria combined with recurrent venous thrombosis events with concluded (deep -hearted venous thrombosis or non -fatal pulmonary embolism) or death related to venous blood tolerance events (see Table 10).

The effectiveness of apixaban in the initial treatment for venous thromboembolism is consistent among patients treated for pulmonary embolism [Risk of relative 0.9; CI 95% (0.5; 1,6)] or deep thrombosis [The risk of walls 0.8; Cl 95% (0.5; 1 '3)].

Effective in sub-groups, including age, gender, 'body mass index-bmi), kidney function, pulmonary embolism, blood clot site in deep veins, and previously heparin injections are generally consistent.

The main evaluation criterion for safety is serious bleeding. In the study, Apixaban is superior to statistics compared to Enoxaparin/Warfarin in the main assessment of safety [Relative Risk) 0.31, 95% reliability (0.17; 0.55), P value

The serious hemorrhage has been concluded and the CRNM bleeding at the surgical position is generally lower in the apixaban group compared to the Enoxaparin/Warfarin group. Serious gastrointestinal bleeding according to ISTH has been concluded in 6 (0.2%) patients treated with apixaban and 17 (0.6%) patients treated with Enoxaparin/Warfarin.

AMPLIFY-Wide amplify research

In the extensive amplify-amplifier study, a total of 2,482 patients are randomly selected for treatment with 2.5 mg apixaban apixaban twice a day orally, 5 mg apixaban twice a day by oral, or placebo for 12 months after completion of 6 to 12 months of initial treatment with anticoagulant drugs.

Of these, 836 patients (33.7%) participated in the amplify research before enrolling in wide amplifying amplify research. The average age is 56.7 and 91.7% of patients who are randomly selected to have an undetent vein thrombosis.

In the study, both doses of apixaban are superior to statistics compared to the fake in the main evaluation criteria of the recurrent recurrent venous thromboembolic embolism (non -fatal deep vein thrombosis or non -fatal pulmonary embolism) or death due to all causes (see Table 12).

The effectiveness of apixaban in preventing recurrent venous thromboembolism is maintained throughout the sub -groups, including age, gender, BMI and kidney function.

The main evaluation criteria for safety is serious bleeding during the research period. In the study, the serious hemorrhage rate for both or the apixaban dose has no statistical difference compared to the price.

There is no significant difference in statistics in serious bleeding rate + CRNM, not serious, and all types of hemorrhage between the group using 2.5 mg apexaban apixaban twice a day and placebo group (see table 13).

Serious gastrointestinal bleeding according to ISTH has been assessed at 1 (0.1%) of patients treated with an apixaban dose of 5 mg twice a day, 0 patients take a dose of 2.5 mg twice a day and 1 (0.1%) patient with placebo.

Dynamic pharmacokinetics

Absorb

The absolute bioavailability of the apixaban is about 50% for a dose of up to 10 mg. Apixaban is quickly absorbed with a maximum concentration (CMAX) that appears 3 to 4 hours after taking the drug. Use with food that does not affect the APixaban CMAX at 10 mg. Apixaban
can be used or not with food.

Apixaban has linear pharmacokinetics with concentration of blood drugs in proportion to the dose, for doses of up to 10 mg orally. At the 225 mg dose, the absorption of the apixaban is limited by the solubility rate, so the bioavailability decreases. The indicators of apixaban concentrations show the variation from low to medium reflected by the coefficients of variation (CV) in each object and between objects are -20% and -30% respectively.

After taking orally 10 mg of apixaban in the form of 2 5 mg tablets crushed to 30 ml of water, the concentration of medication in the blood is similar to the concentration of blood in the blood after taking orally 2 tablets of 5 mg of whole tablets. After using 2 mg of apixaban in the form of 2 crushed 5 -year tablets and 30 g of pureed algae, cmax and reduced in the corresponding level of 20% and 16% compared to when using 2 tablets of 5 mg of whole tablets. This decrease in blood concentration is not considered clinically significant.

After using a 5 mg apixaban apixaban pellet dispersed in 60 ml of D5W and put in a stomach catheter, the concentration of medication in the blood is similar to the concentration of medication in the blood visible in other clinical trials related to healthy people using single -dose apixaban tablets 5 mg.

With the predictable pharmacokinetic properties and proportional to the dosage of the apixaban, the bioavaila results from studies have been conducted can be applied to lower doses of apixaban.

distribution

The ratio of cohesion with plasma proteins in humans is about 87%. The distribution volume (VSS) is about 21 liters.

Biological metabolism and elimination

Apixaban is eliminated through many roads. At the dosage of apixaban used on humans, about 25% are eliminated in the form of metabolites, with most of the waste through the stool.

Eliminate the kidney apixaban accounting for about 27% of the total clearance. Elimination through bile and directly through the intestine is observed in turn in clinical and preclinical studies.

Apixaban has a total clearance of about 3.3 l/hour and the waste time is about 12 hours.

Reduction of 0-methyl group and hydroxylation at 3-Ciperidin groups are the main biological metabolic reactions. Apixaban is metabolized mainly via CYP3A4/5 and a small part through CYP1A2, 28, 2C9, 2019, and 2J2, Apixaban has not metabolized as the main ingredient related to plasma in humans and no metabolites are found in the blood. Apixaban is a substrate of transportation proteins, P-GP and breast cancer protein (BCRP).

kidney failure

impaired renal function does not affect the peak concentration of apixaban. Apixaban's blood concentration increases corresponding to the decline of kidney function, assessing the measurement of creatinine clearance.

In people with mild renal failure (creatinine clearance 51-80 ml/min), average (clearine clearine 30-50 ml/min) and severe (Creatinin clearance 15-29 ml/min), plasma apixaban concentration (AUC) increases 16%, 29% and 44% compared to people with normal creatinine clearance. There is no evidence that renal failure affects the correlation between apixaban concentration in plasma and distant factor activity.

In those who suffer from end -stage Renal Disease (ESRD), the AUC of Apixaban increases to 36% when using the single doses of APixaban 5 mg immediately after blood separation, compared to the observatory found in the object with normal renal function. The hemorrhage begins two hours after taking the single doses of APixaban 5 mg reduces the AUC of the Apixaban 14% on these ESRD objects, corresponding to the apixaban separation of 18 ml/minute. Therefore, hemorrhage is most likely not an effective way to control the overdose of APIXABAN.

liver failure

In a study comparing 8 subjects with mild liver failure, Child-Pough A Point 5 (N = 6) and Point 6 (N = 2), and 8 subjects with average liver failure (Child-Pugh, 3 points 7 (n = 6) and point 8 (n = 2), compare with 16 healthy, pharmacological and dynamic subjects of the single-tempered APIXABANG-MG-mg subjects. The far and INR factor is equivalent to each other between mild and medium liver failure objects and healthy objects.

Elderly

Elderly patients (over 65 years old) have higher plasma concentrations than young patients, with average AUC value about 32% higher and no difference in CMAX.

Sex

Apixaban's blood concentration in women is about 18% higher than men.

ethnic and racial origin

Results through phase 1 studies show a clear difference in the pharmacokinetics of apixaban among whites, Asians and blacks/African -Americans. Analysis of population dynamics on groups of patients using apixaban is generally consistent with the results of phase study.

Body weight

When compared to those who weigh from 65 to 85 kg, the group weighs> 120 kg with apixaban concentration in the blood is about 30% lower and the group weighs

Mobile pharmacokinetic/pharmacokinetic correlation

Pharmacokinetic/pharmacodynamic (PK/PD) between plasma apixaban concentration and many criteria for pharmacological assessment (remote factor activity, Inr, pt, APTT) have been assessed after wide -dose use (0.5 - 50 mg).

The correlation between apixaban concentration in plasma and remote factors is most clearly described by linear model. PK PD correlation is observed in patients consistently with the correlation set in healthy subjects.

Before taking Eliquis 5mg Pfizer prevents the events of venous thrombolytic embolization, stroke (20 tablets)

How to use

Eliquis 5mg oral drug.

Eliquis should be drinked with water, or not cing food. For patients who do not swallow both tablets, Eliquis tablets can be crushed and stirred into water, or 5% in water (DSW), or algae water or mixed with pureed apples and use immediately through oral.In addition, Eliquis tablets can be crushed and stirred into 60 ml. Water or D5W and immediately through the stomach nose. Eliquis tablets are durable in water, D5W, apple juice, and pureed apples for up to 4 hours.

Dosage

Preventing venous thrombosis (VTEP): Surgery to replace hip or knee joints according to the program.

The recommended dosage of apixaban is 2.5 mg oral twice a day. The first dose should be used 12 to 24 hours after surgery.

Doctors may consider the potential benefits of previous anticoagulants to prevent venous thrombolytic events as well as risk of hemorrhagic after surgery when deciding on the time to use the drug during this time frame.

In patients undergoing hip replacement surgery: The recommended treatment time is 32 to 38 days.

In patients undergoing knee replacement surgery: The recommended treatment time is 10 to 14 days.

Prevention of stroke and systemic ganglion in patients with atrial fibrillation due to valve disease (NVAF).

The recommended dosage of apixaban is 5 mg oral 2 times.

Dosage reduction: The dosage of Apixaban is recommended for 2.5 mg oral twice a day in patients with atrial fibrillation due to heart valve disease and at least two of the following characteristics: age> 80, body weight 1.5 mg/dl (133 micromol/l).

Treatment should be maintained for a long time.

Treatment of deep vein thrombosis (DT), pulmonary embolism treatment (PE) and prevention of recurrence DVT and PE (VTE).

The dosage of Apixaban is recommended to treat acute venous thrombosis and pulmonary embolism is 10 mg oral, twice a day for the first 7 days, then 5 mg oral twice a day. According to the current medical instructions, short treatment time (at least 3 months) should be based on temporary risk factors (for example, new surgery, injury, non -moving).

The dosage of apixaban is recommended to prevent recurrence of deep veins and pulmonary embolism is 2.5 mg oral, twice a day. When determining the prevention of recurrence of deep veins and pulmonary embolism, 2.5 mg dose twice a day should be started after 6 months of treatment with 5 mg apixaban twice or with other anticoagulants.

H Bleeding.

Conversion:

Transferring treatments from sugar anticoagulants to Eliquls (and vice versa) can be performed at the time of using the dosage according to the treatment schedule. Do not simultaneously use these drugs.

Transferred from anti -vitamin K treatment (Vitamin Kantagons - VKA) to Eliquis.

When transferring patients from vitamin K (VKA) to Eliquis/Arfarin or other vitamin K anti -Vitamin K medications, they should be stopped and started to use Elquis when the International Normalization Index (INR) is

A trip from Eliquis to anti -vitamin K treatment.

When transferring patients from Eliquis to anti -vitamin K treatment, continue to use Eliquis for at least 2 days after starting treatment with vitamin K anti -vitamin K. Should continue to use Eliquis as the time with the treatment of anti -vitamin K drugs until Inr> 2.

kidney failure:

No need to adjust the dose in patients with mild or medium renal failure.

In patients with severe renal impairment (Creatinine clearance 15-29 ml/minute), apply the following recommendations:

To prevent venous thrombolytic embolism in the surgery to replace cave or knee joints under the program (VTEP), the treatment of deep vein thrombosis (DVT), the treatment of embryonic embryo and prevention of deep veins recurrence and pulmonary embolism (VTEP), apixaban must be used carefully;

To prevent mutant and body vascular obstruction in patients with atrial fibrillation without valve disease (NVAF):

Patients should take lower doses of Apixaban is 2.5 mg twice a day. ml/minute, or in patients undergoing dialysis, no clinical experience, so the apixaban is not recommended.

Hepatic failure:

Eliquis is contraindicated in patients with liver disease related to clots and the risk of clinical significance.

This drug is not recommended for patients with severe liver failure.

This drug should be used carefully in patients with mild or medium liver failure (Childpugh a host b). Do not adjust the dose in patients with mild or medium liver failure.

Patients with Alanin Aminotransferase (ALT) /Aspartat Aminotransferase (AST) (AST) 2 x ULN (the upper limit of normal level) or overall bilirubin> 1.5 x DLN have been excluded in blue tests. Therefore, Eliquis must be used cautiously in this patient group. Before starting to use Eliquis, you should see off the liver function test.

Body weight:

Prevention of venous thromboembolism (VTEP) and treatment of deep vein thrombosis, treatment of pulmonary embolism and prevention of recurrence of deep veins and pulmonary embolism (VTEUT) - No dose adjustment.

Patients with atrial fibrillation due to valve disease: do not carefully adjust the dose, unless satisfied the dose criteria.

Sex: No need to adjust the dose by gender.

Elderly: Prevention of venous thromboembolism (VTEP) and deep vein thrombosis, embryo embryo treatment and prevention of deep vein recurrence and embryonic embryo (VTEI) - No need to adjust the dose.

Patients with atrial fibrillation due to valve disease: No dose adjustment, unless satisfied the criteria of willow reduction.

Heart rate restoration (in patients with atrial fibrillation due to heart valve disease): Patients continue to use apixaban while being carried out of cardioversion.

Pediatric patients: The safety and effectiveness of Eliquis have not been determined in children and teenagers under 18.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What to do when overdose? Overdose of apixaban can lead to a higher risk of bleeding. In case of hemorrhage complications, treatment must be discontinued and investigate the cause of hemorrhage.

Conducting appropriate treatment, for example, hemostasis in surgery or fresh frozen plasma should be considered.

In control clinical trials, using oral apixaban on a healthy statue with a maximum dose of up to 50 mg daily from 3 to 7 days (25 mg twice a day for 7 days or 50 mg once a day in 3 days) has no clinical significance.

In healthy subjects, using activated carbon from 2 to 6 hours after taking a dose of 20 mg of apixaban, reducing by 50% and 27% of the average AUC of the apixaban and does not affect CMAX. The average Thai version of Apixaban decreased from 13.4 hours when Apixaban was used separately 5.3 hours and 4.9 hours, respectively when using activated carbon after 2 and 6 hours of using Apixaban. Therefore, using activated carbon can be useful in the treatment of apixaban overdose or accidentally swallowing apixaban.

If the life -threatening bleeding cannot be controlled by the aforementioned measures, it is possible to consider using a concentrated prothrombin complex or recombinant vila element.

The reversal of Eliquis has been reversed, as shown by the changes in the thrombin production test at the end of the process of transmitting and achieving the initial value within 4 hours after the beginning of the 4 -minute PCC transmission process in 30 minutes in healthy objects.

However, there is no clinical experience in the use of 4-PCC products to reverse the bleeding process in patients using Eliquis.

There is no experience in using VHA factors to load combinations in patients using apixaban. It is possible to consider and adjust or determine the dose for the recombinant factor depending on the improved hemorrhage situation.

If there is an expert at the grassroots level, they should consider their consultation about coagulation in case of serious bleeding.

Hemorrhage hemorrhage reduces 14% AUC of Apixaban in end -stage kidney disease (ESRD), when a 5 mg APixaban single dose is used by oral. Therefore, blood separation is most likely not a effective way to overdose apixaban.

In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

Side Effects

When using Eliquis, you may experience unwanted effects (ADR).

Summary of safety

The safety of Apixaban has been studied in 7 clinical studies III including more than 21,000 patients: More than 5,000 patients in studies to prevent venous thrombolytic embolism (VTEP), more than 11,000 patients in non -valve -hearted atrial studies and more than 4,000 patients in the studies of viscous treatment of venous thrombolytilation (VTED, with average medication time are 20 years, 1.7 years and 221 years, 1.7 years and 221 years, 1.7 years and 221 years, 1.7 Date.

Unwanted effects are bleeding, bruises, nosebleeds, and hematoma.

In studies to prevent venous thrombosis (VTEP), a total of 11% of patients treated with Apixaban 2.5 mg twice a day have unwanted effects.

The overall ratio of unwanted effects related to hemorrhage when using apixaban is 10% in the study of apixaban comparison with enoxaparin.

In non -valve atrial fibrillation studies, the overall ratio of unwanted effects related to hemorrhage when using apixaban is 24.3% in apixaban comparison research with warfarin and 9.6% in apixaban comparison research with acetylsalicylic acid.

In the study of apixaban comparison with Warfarin, the ratio of serious digestion hemorrhage according to ISTH (including upper digestive tract, lower digestive tract, and rectal hemorrhage) when using apixaban is 0.76%/year. The ratio of serious intraocular hemorrhage according to ISTH when using apixaban is 0.18%/year.

In studies for treating venous thrombosis (VTET, the overall frequency of unwanted effects related to bleeding when using apixaban is 15.6% in apixaban comparison research with enoxaparin/warfarin and 13.3% in apixaban comparison research with fake.

List of unwanted effects

Table 2 shows unwanted effects arranged according to the organs classification and frequency, using the following conventions: Very common (≥ 1/10); Common (≥ 1/100 to

Report unexpected effects

Reporting undoubtedly unwanted effects after the drug is approved is very important. This allows to continue monitoring the balance between the benefits/risks of the drug. Medical experts are encouraged to report any suspicious unwanted effects.

Instructions on how to handle ADR

When experiencing side effects of the drug, patients need to stop using and notify the doctor or go to the nearest medical facility for timely treatment.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

Contraindicated

Elaquis 5mg contraindications in the following cases:

Hypersensitivity to active ingredients or any excipients. This may include existing gastrointestinal ulcers or recently, the presence of malignant tumors is at high risk of hemorrhage, recent brain or spine damage, recent brain, spine or eye surgery, recent intracranial hemorrhage, known or suspected esophageal varicose veins, venous dynamic deformities, blood vessel aneurysms or serious intracellular or intracellular veins. Heparin is not segmented (UFH), low molecular weight heparin (enoxaparin, dalteparin ...), Heparin's derivatives (fondaparinux ...), oral anticoagulants (Warfarin, Rivaroxaban, Dabigatran ...) except cases of specific anti -coagulation drugs or when UFH is used in the dose needed to keep the dose necessary Or the central artery is ventilated.

Be cautious when using

need to be very careful when taking the drug for patients in the following cases:

Hemorrhage risk

Like other anticoagulants, patients using Eliquis should be carefully monitored with signs of bleeding. This drug should be used with caution with increased hemorrhage risk.

Need to stop using Eliquis if severe bleeding.

Although the treatment with Apixapan does not require regular monitoring of blood concentrations in the blood, the quantitative testing test is the calibration anti-factor that can be useful in special cases when knowing the concentration of apixaban in the blood can help clinical decisions, such as overdose and emergency surgery.

Interaction with other drugs affects hemostasis

Due to the increased risk of bleeding, contraindicated treatment simultaneously with any other anticoagulant drugs.

Concomitant use of Eliquis with platelet resistant increases the risk of bleeding.

Be cautious if the patient is treated simultaneously with non-steroidal anti-inflammatory drugs (non-steroidal anti-inflammatory drugs (NSAID), including acetylsalicylic acid.

After surgery, other platelet aggregation inhibitors should not be used at the same time with Eliquis.

In patients with atrial fibrillation and the need for single or dual -demand resistance therapy, careful assessment of potential benefits compared to the risks may be encountered before combining this therapy with Eliquis.

In a clinical trial in patients with atrial fibrillation, simultaneous use with aspirin (Asa) increases the risk of serious bleeding of apixaban from 1.8% a year to 3.4% a year and increases the risk of bleeding of Warfarin Tig 2, 7% a year to 4.6% a year.

In this clinical trial, simultaneous use with dual platelet resistance is not much (2.1%).

In a clinical trial in patients with high risk peel syndrome, there are many characteristics that are accompanied by heart -related diseases and not related to the heart, are used for aspirin or combining aspirin and clopidogrel, a sign that significantly increases the risk of serious bleeding according to ISTH (International Association of Blood Blood and Hematoma) with apixaban (5.13% per year) year).

Use blood soluble substances to treat acute ischemic stroke

There is little experience in the use of thrombolytic substances to treat stroke due to acute ischemia in patients who are used apixaban.

Patients using artificial cardiac valves

The safety and effectiveness of Eliquis has not been studied in patients with artificial cardiac valves, attached or without atrial fibrillation. Therefore, the use of Eliquis is not recommended in this case.

surgery and invasive procedures

Eliquis needs to be discontinued at least 48 hours before surgery under the program or invasive procedure that is at risk of average or high bleeding. These surgeries or tricks include interventions with significant probability of bleeding, which cannot be excluded or have an unacceptable risk of bleeding.

Eliquis needs to be stopped at least 24 hours before performing surgery under the program or invasive procedure at risk of low bleeding. These surgeries or tricks include the expected interventions that arise negligible bleeding, not serious in hemorrhage or easy to control.

If surgery or invasive procedure cannot be delayed, be careful and pay attention to the risk of bleeding. The risk of bleeding should be considered compared to the urgency of intervention.

Eliquis should be started for reuse after conducting invasive procedures or intervention by surgery as soon as possible as long as the clinical condition is allowed and the bleeding is appropriate with cardioverions.

Temporary medicine stops

Discontinuing the use of anticoagulant drugs, including Eliquis, during bleeding, surgery according to the program, or invasive procedure, the patient will be placed in an increased risk of thrombosis. It is necessary to avoid stopping the medication during treatment and if it is necessary to suspend the use of anticoagulants with Eliquis for any reason, it is necessary to start treatment as soon as possible.

Anesthesia or poking of epidural spinal cord

When conducting anesthesia of cerebrospinal axis (spinal/spinal anesthesia) or spinal cord/dumping, patients are treated with anticoagulants to prevent vascular obicient complications due to thrombosis, which is at risk of hematoma or spinal cord, which can lead to long -term or permanent paralysis.

The risk of these events may increase due to postoperative external surgical ducts or simultaneous use with other drugs that affect blood clotting. Mr. Thong in epidural or endocardium must be removed at least 5 hours before the first dose of Eliquis.

The risk may also be increased by epidural damage or fibromy or spinal cord repeated. Patients should be monitored regularly to find signs or symptoms of nerve damage (for example, numb or weak legs, intestinal dysfunction or bladder).

If the nerve damage is recorded, it is necessary to diagnose and treat emergency treatment. Before interfering with the cerebrospinal axis, the doctor needs to consider the potential benefits compared to the risk in patients using anticoagulants or patients will be anti -coagulation in the treatment of blood thrombosis.

There is no clinical experience on the use of apixaban with the placement of an external or endometrial duct. In case of this need and based on the general pharmacokinetic characteristics of the apixaban, it is necessary to wait for a period of 20-30 hours (ie 2 x time
the waste time) between the last apixaban dose and the time of drainage of the drainage pipe, and skip at least one dose before removing the drain. It is possible to use the next apixaban dose for at least 5 hours after removing the drain.

Like all new anticoagulants, there is very little experience in anesthesia on the cerebrospinal axis and therefore should be extremely careful when using apixaban in case of anesthesia into the cerebrospinal axis.

patients with unstable hemodynamic pulmonary pulmonary disease or patients need to soluble thrombosis or tricks to eliminate thrombosis in the lungs

Do not use eliquis instead of non -segmented heparin in patients with unstable hemodynamic pulmonary embolism or can be dissolved in thrombosis or tips to eliminate thrombosis in the lungs because it has not established the safety and effectiveness of apixaban in these clinical situations.

Patients with cancer are in progress

Not yet established the effectiveness and safety of apixaban in the treatment of deep vein thrombosis, treatment of pulmonary embolism and preventing deep vein thrombosis and pulmonary embolism (VTET) in patients with progressive cancer.

Patients with renal failure

Very few clinical data shows that apixaban concentration in plasma increases in patients with severe renal impairment (clearine clearine 15-29 ml/minute) is a condition that can lead to increased risk of bleeding.

To prevent venous thrombolytic embolism in the hip or knee joint replacement surgery (VTEP), the treatment of deep vein thrombosis (DVT), pulmonary embolism treatment (PE) and prevention of deep vein recurrence and pulmonary embolism (VTET), careful use of apixaban in patients with severe renal insufficiency (15-29 mL/minute clearance).

To prevent stroke and body embolism in patients with atrial fibrillation due to non-valve disease, patients with severe renal impairment (creatinine clearance 15-20 ml/minute), and patients with serum creatinine 1.5 mg/dl 133 micromol/l) and over 80 years old or body weight In patients with creatinine clearance

Elderly patients

Old age may increase the risk of bleeding. Also, be careful when using Eliquis with aspirin in elderly patients because of the higher risk of bleeding.

Body weight

Low body weight (

Patients with liver failure

Eliquis is contraindicated in patients with liver disease associated with coagulation disorders and the risk of hemorrhage of clinical significance.

Do not use for patients with severe liver failure.

Should be cautious when used for patients with mild or medium liver failure (Child-Pugh A or B).

Patients with Alt/AST liver enzymes increase> 2 x ULN (the upper limit of normal level) or overall bilirubin> 1.5 x ULN has been removed from clinical trials. So Eliquis should be used cautiously for this group. Before starting to use Eliquis, it is recommended to conduct liver function tests.

Interacts with the inhibitor of both Cochrom P450 3A4 (CYP3A4) and P-Glycoprotein (P-GP)

Do not use Eliquis for patients being treated with the whole body simultaneously with the strong inhibitors of both CYP3A4 and P-GP, such as antifungal drugs Azol (for example, ketoconazol, otraconazole, voriconazole and posaconazole) and enzyme inhibitors HIV (for example, ritonavir). These drugs may increase the concentration of apixaban in the blood 2 times, or more in the case of additional factors that increase the concentration of apixaban in the blood (for example, severe kidney failure).

Interaction with the induction substance of both CYP3A4 and P-GP

Simultaneous use Eliquis with strong induction substances CYP3A4 and P -GP (for example, Rifampicin, Phenytoin, Carbamazepin, Phenobarbital or St. John's Wort) can cause apixaban levels in the blood to decrease by -50%. In a clinical study in atrial fibrillation patient,
found that the effectiveness and the risk of bleeding were higher when using apixaban with strong induction substances of both CYP3A4 and P-GP compared to when only for apixaban.

In patients treated the whole body simultaneously with the strong induction substances of both CYP3A4 and P-GP, applying the following recommendations:

To prevent venous thrombolytic embolism in hip or knee joint replacement surgery, to prevent stroke and systemic embolism in patients with atrial fibrillation due to heart valve disease and to prevent relapse of deep veins and pulmonary embolism, should be cautious when using apixaban;

To treat deep vein thrombosis and treat pulmonary embolism, apixaban should not be used due to effectiveness may be affected.

Hirgonary fracture surgery

Apixaban has not been studied in clinical trials in patients undergoing surgery to treat hip fractures to evaluate the effectiveness and safety in these patients. Therefore, should not be used for these patients.

Testing indicators

Blood coagulation test [for example, the time of prothrombin (pt), INR, and thromboplastin time (APTT) (APTT)] is expected to be affected by APixaban's operating mechanism.

The observed changes found in blood clotting tests at the dose of treatment are small and highly variable.

Information about excipients

Eliquis contains lactose. Patients with rare genetic problems about galactose intolerance, Lapp Lactase deficiency, or Glucose-Galactose should not use this drug.

affect fertility, pregnant and lactating women

Pregnant women

There is no data on the use of apixaban in pregnant women. Animal studies do not show direct or indirect harm to toxicity to reproductive function.

Apixaban is not recommended for use during pregnancy.

breastfeeding women

whether the apixaban and its metabolites are secreted through human milk or not. The data available on animals shows that apixaban has milk. In rat milk, realize that the percentage of drugs in milk compared to the plasma of the mother is high (CMAX is approximately 8, AUC is approximately 30), maybe due to the actual process of transporting drugs into milk.

The risk of babies and young children cannot be excluded. Need to decide to stop breastfeeding or stop/avoid using apixaban therapy.

fertility

Animal studies used for apixaban have shown that there is no influence on fertility.

The image is aimed at driving and operating machinery

Eliquis does not affect or negatively affect the ability to drive and operate machinery.

Drug interaction

drug interactions may affect the activity of the drug or cause side effects. Should notify the doctor or pharmacist a list of drugs and functional foods you are using. Do not use or increase or decrease the dose of the drug without the guidance of a doctor.

inhibitors of CYP3A4 and P-GP

Apixaban is used with ketoconazole (400 mg once a day), a strong inhibitor of both CYP3A4 and P-GP, resulting in an increase of 2 times the average of Apixaban and 1.6 times the average cmax of APIXaban.

Do not use Eliquis for patients being treated with the whole body simultaneously with the strong inhibitors of CYP3A4 and P-GP coffee, such as antifungal drugs Azol (for example, ketoconazol, otraconazole, voriconazole and posaconazole) and enzyme inhibitors of HIV (for example, ritonavir)).

The active ingredients are not considered strong inhibitors of both CYP3A4 and P-GP, (for example, Diltiazem, Naproxen, Amiodaron, Verapamil, Quinidine) are expected to increase the sequence of apixaban in plasma at a lower level. For example Diltiazem (360 mg once a day) is considered a
average inhibitor of CYP3A4 and the slight inhibitor of the P-GP, resulting in an increase of 1.4 times the average and an increase of 1.3 times cmax of Apixaban. Naproxen (500 mg, single dose), an inhibitor of P-GP but does not inhibit CYP3A4, resulting in 1.6 times and 1.6 times in the average AUC and CMAX of Apixaban.

Not to adjust the apixaban dose when used simultaneously with less effective inhibitors of CYP3A4 and/or P-GP

The induction substance of CYP3A4 and P-GP

Apixaban simultaneously used with rifampin, a strong induction substance of both CYP3A4 and P-GP, resulting in a decrease of about 54% and 42% corresponding to the average and CMAX CMAX of Apixaban. Simultaneous use of apixaban with other strong induction substances of CYP3A4 and subtitards (for example, phenytoin, carbamazepin, phenobarbital or st.

No need to adjust the dose of apixabanfong the treatment process simultaneously with these drugs, but in patients treated the whole body simultaneously with the strong induction substances of both CYP3A4 and P-GP, should be cautious when using apixaban to prevent venous thrombolytic embolism in replacement of groin or knee joints according to the heart-shapes, preventing the body with a stem of the patient with a stem heart disease and prevent recurrence of deep veins and pulmonary embolism.

Do not use apixaban to treat deep vein thrombosis and pulmonary embolism in patients who are treated with the whole body simultaneously with the strong induction substances of both CYP3A4 and P-GP because the effectiveness can be affected.

anticoagulant drugs, platelets inhibitors and NSAIDs

Due to the increased risk of bleeding, contraindicated treatment simultaneously with any other anticoagulants.

After using the combination of Enoxaparin (40 mg of single dose) with apixaban (5 mg of single dose), observed the impact of copper on the distance of the distant factor.

Mobile interactions or pharmacodynamics are not clear when apixaban is used simultaneously with aspirin 325 mg once a day.

Apixaban is simultaneously used with clopidogrel (75 mg once a day) or with a combination of Clopidogrel 75mg and Aspirin 162 mg once a day, or with prasugrel (60 mg later 10 mg once a day) in phase I do not show increased bleeding time, or increase inhibition of related platelets relevant to anti -platelet drugs at the same time with anti -platelets with apology. The phenomenon of indicators in blood clotting tests (PT, INR and APTT) increases in accordance with the effects of apixaban when used in single.

Naproxen (500 mg), a P-GP inhibitor to an increase of 1.5 times and 1.6 times corresponding to the average AUC and CMAX, of the apixaban. The corresponding increase in blood clotting tests are observed in the apixaban. No change has been observed about the effects of Naproxen on plateletic collection caused by arachidonic acid and clinically, there is no related prolongation of the hemorrhage time is observed after simultaneous use of apixaban and naproxen.

Despite these findings, there may still be people who have a clearer force when platelets are used with Apixaban. Should be cautious when using simultaneously Eliquis with NSAID (including acetylsalicylic acid) because these drugs often increase the risk of bleeding. There is a significant increase in the risk of hemorrhage combining three drugs apixaban, aspirin and clopidogrel in a clinical study in patients with acute coronary syndrome.

Do not simultaneously use drugs related to serious bleeding with Eliquis, such as: Blood soluble substances, antagonists of GPIIB/IIIA, Thienopyridine (e.

Other simultaneous therapies

There is no pharmacokinetic interaction or any clinical significance that is observed when the apixaban is simultaneously used with Atenolol or Famotidin.

Apixaban 10 mg is concentrated with Atenolol 100 mg without any clinical significance with pharmacokinetics of Apixaban. After taking two drugs together, the average AUC and CMAX Cu Apixaban are 15% and 18% lower than when using their own apixaban.

Apixaban 10 mg is used with Famotidin 40 mg does not affect rust or cmax of apixaban.

The effect of apixaban on other drugs

Research on Apixaban In Vitro shows no inhibitory effect on the operation of CYPLA2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (ICSO> 45 Um) and have weak inhibitors for the operation of CYP2C19 (ICSO> 20 WM) Hematoma is observed on patients.

Apixaban does not cause CYP1A2, CYP2B6, CYP3A4/5 at a concentration of up to 20 µm. Therefore, Apixaban is expected to change the clearance of the transformation of the drugs used simultaneously transformed by these enzymes.

Apixaban is not a significant inhibitor of P-GP. In studies on the healthy object as described below, Apixaban does not change the pharmacokinetics of Digoxin, Naproxen or Atenolol in a meaningful way.

digoxin

Apixaban (20 mg once a day) is used simultaneously with digoxin (0.25 mg once a day), a substrate of P-GP, does not affect the AUC or CMAX of Digoxin. Therefore, apixaban does not inhibit the transportation of substrate through the intermediary P-GP.

naproxen

Apixaban (10 mg) single dose simultaneously with Naproxen (500 mg), an NSAID is commonly used, without any effect on AUC or CMAX of Naproxen.

atenolol

Apixaban (10 mg) single dose simultaneously with Atenolol (100 mg), a popular beta blocker, does not change the pharmacokinetics of Atenolol.

activated carbon

For activated carbon use reduces apixaban.

Storage

Leave a cool place, avoid light, temperature below 30⁰C.

Other drugs

Disclaimer

Every effort has been made to ensure that the information provided by Drugslib.com is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Drugslib.com information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Drugslib.com does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Drugslib.com's drug information does not endorse drugs, diagnose patients or recommend therapy. Drugslib.com's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Drugslib.com does not assume any responsibility for any aspect of healthcare administered with the aid of information Drugslib.com provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.