Apixaban

(a pix' a ban)

Molecule Info

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WARNING

DISCONTINUING Apixaban IN PATIENTS WITHOUT ADEQUATE CONTINUOUS ANTICOAGULATION INCREASES RISK OF STROKE

Discontinuing Apixaban places patients at an increased risk of thrombotic events. An increased rate of stroke was observed following discontinuation of Apixaban in clinical trials in patients with nonvalvular atrial fibrillation. If anticoagulation with Apixaban must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered.

ATC Classification B01A - Apixaban, ANTITHROMBOTIC AGENTS; Used in the treatment of thrombosis.
Description
Apixaban contains the following excipients: Tablet Core: Anhydrous lactose, mycrocrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, magnesium stearate.  Film Coat: Lactose monohydrate, hypromellose, titanium dioxide, triacetin, yellow iron oxide.
Indication(s) Prevention of venous thromboembolic events in adult patients who have undergone elective hip or knee replacement surgery.
Dosage & Administration

The recommended dose of Apixaban is 2.5 mg taken orally twice daily.  The initial dose should be taken 12-24 hrs after surgery. Physicians may consider the potential benefits of earlier anticoagulation for VTE prophylaxis as well as the risks of post-surgical bleeding in deciding on the time of administration within this time window. 

Patients Undergoing Hip Replacement Surgery: The recommended duration of treatment is 32-38 days. 

Patients Undergoing Knee Replacement Surgery: The recommended duration of treatment is 10-14 days. If a dose is missed, the patient should take Apixaban immediately and then continue with twice-daily intake as before. Switching treatment from parenteral anticoagulants to apixaban can be done at the next scheduled dose. 

Renal Impairment: Because there is no clinical experience in patients with CrCl <15 mL/min, or in patients undergoing dialysis, apixaban is not recommended in these patients.  Limited clinical data in patients with severe renal impairment indicate that apixaban plasma concentrations are increased in this patient population; therefore, apixaban is to be used with caution in these patients. No dose adjustment is necessary in patients with mild or moderate renal impairment. 

Hepatic Impairment: Apixaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. It is not recommended in patients with severe hepatic impairment. It should be used with caution in patients with mild or moderate hepatic impairment.  No dose adjustment is required in patients with mild or moderate hepatic impairment. Patients with elevated liver enzymes or total bilirubin ≥1.5 x ULN were excluded in clinical trials.  Therefore, apixaban should be used with caution in this population.  ALT should be measured as part of the standard pre-operative evaluation. 

Elderly: No dose adjustment required. Body Weight: No dose adjustment required. Gender: No dose adjustment required. 

Administration: Oral use. Apixaban should be swallowed with water, with or without food.

Overdosage
There is no antidote to Apixaban.  Overdose of apixaban may result in a higher risk of bleeding.  In the event of haemorrhagic complications, treatment must be discontinued and the source of bleeding investigated.  The initiation of appropriate treatment, eg, surgical haemostasis or the transfusion of fresh frozen plasma should be considered. In controlled clinical trials, Oral  ly administered apixaban in healthy subjects at doses up to 50 mg daily for 3-7 days  had no clinically relevant adverse effects. A preclinical study in dogs demonstrated that Oral   administration of activated charcoal up to 3 hrs after apixaban administration reduced apixaban exposure; therefore, activated charcoal may be considered in the management of apixaban overdose. If life-threatening bleeding cannot be controlled by the previously mentioned measures, administration of recombinant factor VIIa may be considered.  However, there is currently no experience with the use of recombinant factor VIIa in individuals receiving apixaban.  Re-dosing of recombinant factor VIIa could be considered and titrated depending on improvement of bleeding. 
Contraindication(s)
Hypersensitivity to apixaban or to any of the excipients. Clinically significant active bleeding. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk.
Precaution(s) and use in Specific Population

Haemorrhage Risk: As with other anticoagulants, patients taking Apixaban are to be carefully observed for signs of bleeding.  It is recommended to be used with caution in conditions with increased risk of haemorrhage eg, congenital or acquired bleeding disorders, active ulcerative gastrointestinal disease, bacterial endocarditis, thrombocytopenia, platelet disorders, history of haemorrhagic stroke, severe uncontrolled hypertension, and recent brain, spinal, or ophthalmological surgery.  Apixaban administration should be discontinued if severe haemorrhage occurs. Renal Impairment: Because there is no clinical experience in patients with CrCl <15 mL/min, or in patients undergoing dialysis, apixaban is not recommended in these patients. Limited clinical data in patients with severe renal impairment indicate that apixaban plasma concentrations are increased in this patient population; therefore, apixaban alone or in combination with acetylsalicylic acid is to be used with caution in these patients because of a potentially higher bleeding risk. No dose adjustment is necessary in patients with mild or moderate renal impairment. Hepatic Impairment: Apixaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. It is not recommended in patients with severe hepatic impairment. It should be used with caution in patients with mild or moderate hepatic impairment. Patients with elevated liver enzymes ALT/AST >2 x ULN or total bilirubin ≥1. 5 x ULN were excluded in clinical trials.  Therefore, Apixaban should be used cautiously in this population.  Alanine aminotransferase should be measured as part of the standard pre-operative evaluation. Interaction with Inhibitors of Both Cytochrome P450 3A4 and P-glycoprotein: The use of Apixaban is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp eg, azole-antimycotics and HIV protease inhibitors.  These medicinal products may increase apixaban exposure by ≥2-fold in the presence of additional factors that increase apixaban exposure. Interaction with Inducers of Both CYP3A4 and P-gp: The concomitant use of Apixaban with strong CYP3A4 and P-gp inducers may lead to approximately 50% reduction in apixaban exposure.  Strong inducers of both CYP3A4 and P-gp should be co-administered with caution. Interaction with Other Medicinal Products Affecting Haemostasis: Care is to be taken if patients are treated concomitantly with nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid.  Other platelet aggregation inhibitors or other antithrombotic agents are not recommended concomitantly with Apixaban. Spinal/Epidural Anaesthesia or Puncture: When neuraxial anaesthesia or spinal/epidural puncture is employed, patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal haematoma which can result in long-term or permanent paralysis.  The risk of these events may be increased by the post-operative use of indwelling epidural catheters or the concomitant use of medicinal products affecting haemostasis.  Indwelling epidural or intrathecal catheters must be removed at least 5 hrs prior to the 1st dose of Apixaban.  The risk may also be increased by traumatic or repeated epidural or spinal puncture.  Patients are to be frequently monitored for signs and symptoms of neurological impairment.  If neurological compromise is noted, urgent diagnosis and treatment is necessary.  Prior to neuraxial intervention, the physician should consider the potential benefit versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis. There is no clinical experience with the use of apixaban with indwelling intrathecal or epidural catheters.  In case there is such need and based on PK data, a time interval of 20-30 hrs between the last dose of apixaban and catheter withdrawal should elapse, and at least 1 dose should be omitted before catheter withdrawal.  The next dose of apixaban may be given at least 5 hrs after catheter removal.  As with all new anticoagulant drugs, experience with neuraxial blockade is limited and extreme caution is therefore recommended when using apixaban in the presence of neuraxial blockade. Hip Fracture Surgery: Apixaban has not been studied in clinical trials in patients undergoing hip fracture surgery to evaluate efficacy and safety in these patients.  Therefore, it is not recommended in these patients. Laboratory Parameters: Clotting tests are affected as expected by the mechanism of action of apixaban.  Changes observed in these clotting tests at the expected therapeutic dose are small and subject to a high degree of variability. Excipients: Apixaban contains lactose.  Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take Apixaban. Effects on the Ability to Drive or Operate Machinery: Apixaban has no or negligible influence on the ability to drive and use machines. 

Impairment of Fertility: Studies in animals dosed directly with apixaban have shown no effect on fertility.  However, in the female offspring of pregnant rats treated with apixaban, there were decreases in mating and fertility. 

Use in pregnancy: There are no data from the use of apixaban in pregnant women.  Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.  Apixaban is not recommended during pregnancy. 

Use in lactation: It is unknown whether apixaban or its metabolites are excreted in human milk.  Available data in animals have shown excretion of apixaban in milk.  In rat milk, a high milk-to-maternal plasma ratio was found, possibly due to active transport into the milk.  A risk to newborns and infants cannot be excluded. A decision must be made to either discontinue breastfeeding or to discontinue/abstain from apixaban therapy. 

Use in children: The safety and efficacy of Apixaban in children <18 years have not been established.  No data are available. 

Use in the elderly: There is limited clinical experience in elderly patients co-administered Apixaban with acetylsalicylic acid.  This combination should be used cautiously because of a potentially higher bleeding risk.

Adverse Drug Reaction(s) The safety of apixaban has been evaluated in 1 phase II and 3 phase III studies including 5924 patients exposed to apixaban 2. 5 mg twice daily undergoing major orthopaedic surgery of the lower limbs treated for up to 38 days. In total, 11% of the patients treated with apixaban 2. 5 mg twice daily experienced adverse reactions.  As with other anticoagulants, bleeding may occur during apixaban therapy in the presence of associated risk factors eg, organic lesions liable to bleed.  Common adverse reactions were anaemia, haemorrhage, contusion, and nausea.  The adverse reactions should be interpreted within the surgical setting. As with any anticoagulant, the use of Apixaban may be associated with an increased risk of occult or overt bleeding from any tissue or organ, which may result in posthaemorrhagic anaemia.  The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding.
Drug Interaction(s)
Inhibitors of CYP3A4 and P-gp: Co-administration of apixaban withketoconazole, a strong inhibitor of both CYP3A4 and P-gp, led to a 2-fold increase in mean apixaban AUC and a 1. 6-fold increase in mean apixaban Cmax.  The use of Apixaban is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp eg, azole-antimycotics and HIV protease inhibitors.  Active substances moderately inhibiting the apixaban elimination pathways, CYP3A4 and/or P-gp, are expected to increase apixaban plasma concentrations to a lesser extent.  Diltiazem, for instance, considered a moderate CYP3A4 and a weak P-gp inhibitor, led to a 1. 4-fold increase in mean apixaban AUC and a 1. 3-fold increase in Cmax.  Naproxen an inhibitor of P-gp but not an inhibitor of CYP3A4, led to a 1. 5-fold and 1. 6-fold increase in mean apixaban AUC and Cmax, respectively.  No dose adjustment for apixaban is required when co-administered with less potent inhibitors of CYP3A4 and/or P-gp. Inducers of CYP3A4 and P-gp: Co-administration of apixaban with rifampicin, a strong inducer of both CYP3A4 and P-gp, led to an approximate 54% and 42% decrease in mean apixaban AUC and Cmax, respectively.  The concomitant use of apixaban with other strong CYP3A4 and P-gp inducers may also lead to reduced apixaban plasma concentrations.  No dose adjustment for apixaban is required during concomitant therapy with such agents; however, strong inducers of both CYP3A4 and P-gp should be co-administered with caution. Anticoagulants: After combined administration of enoxaparin with apixaban, an additive effect on anti-Factor Xa activity was observed. Due to an increased bleeding risk, care is to be taken if patients are treated concomitantly with any other anticoagulants. Platelet Aggregation Inhibitors and NSAIDs: Pharmacokinetic or pharmacodynamic interactions were not evident when apixaban was co-administered with acetylsalicylic acid 325 mg once a day. Apixaban co-administered with clopidogrel or with the combination of clopidogrel 75 mg and acetylsalicylic acid 162 mg once daily in phase 1 studies did not show a relevant increase in template bleeding time, platelet aggregation, or clotting tests compared to administration of the antiplatelet agents without apixaban. Naproxen, an inhibitor of P-gp, led to a 1. 5-fold and 1. 6-fold increase in mean apixaban AUC and Cmax, respectively.  Corresponding increases in clotting tests were observed for apixaban.  No changes were observed in the effect of naproxen on arachidonic acid-induced platelet aggregation and no clinically relevant prolongation of bleeding time was observed after concomitant administration of apixaban and naproxen. Despite these findings, there may be individuals with a more pronounced pharmacodynamic response when antiplatelet agents are co-administered with apixaban.  Apixaban should be used with caution when co-administered with NSAIDs because these medicinal products typically increase the bleeding risk.  A significant increase in bleeding risk was reported with the triple combination of apixaban, acetylsalicylic acid andclopidogrel in a clinical study in patients with acute coronary syndrome.  Agents associated with serious bleeding are not recommended concomitantly with Apixaban eg, unfractionated heparins and heparin derivatives [including low molecular weight heparins ], factor Xa-inhibiting oligosacchrides, direct thrombin II inhibitors, thrombolytic agents, GPIIb/IIIa receptor antagonists, thienopyridines, dipyridamole,dextran, sulfinpyrazone, vitamin K antagonists, and other Oral   anticoagulants. Other Concomitant Therapies: No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when apixaban was co-administered with atenolol or famotidine.  Co-administration of apixaban 10 mg with atenolol 100 mg did not have a clinically relevant effect on the pharmacokinetics of apixaban.  Following administration of the 2 medicinal products together, mean apixaban AUC and Cmax were 15% and 18% lower than when administered alone.  The administration of apixaban 10 mg with famotidine 40 mg had no effect on apixaban AUC or Cmax. Effect of Apixaban on Other Medicinal Products: In vitro apixaban studies showed no inhibitory effect on the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 and weak inhibitory effect on the activity of CYP2C19 at concentrations that are significantly greater than peak plasma concentrations observed in patients.  Apixaban did not induce CYP1A2, CYP2B6, CYP3A4/5 at a concentration up to 20 micromolar.  Therefore, apixaban is not expected to alter the metabolic clearance of co-administered drugs that are metabolized by these enzymes.  Apixaban is not a significant inhibitor of P-gp. In studies conducted in healthy subjects, as described in the following text, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, or atenolol. Digoxin: Co-administration of apixaban and digoxin, a P-gp substrate, did not affect digoxin AUC or Cmax.  Therefore, apixaban does not inhibit P-gp mediated substrate transport. Naproxen: Co-administration of single doses of apixaban and naproxen, a commonly used NSAID, did not have any effect on the naproxen AUC or Cmax. Atenolol: Co-administration of a single dose of apixaban and atenolol, a common β-blocker, did not alter the pharmacokinetics of atenolol.
Pharmacology

Pharmacodynamics

Mechanism of Action:

Apixaban is a potent, Oral, reversible, direct and highly selective active site inhibitor of factor Xa.  It does not require antithrombin III for antithrombotic activity.  Apixaban inhibits free and clot-bound factor Xa, and prothrombinase activity.  Apixaban has no direct effects on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin.  By inhibiting factor Xa, apixaban prevents thrombin generation and thrombus development.  Preclinical studies of apixaban in animal models have demonstrated antithrombotic efficacy in the prevention of arterial and venous thrombosis at doses that preserved haemostasis. Pharmacodynamic Effects: The pharmacodynamic effects of apixaban are reflective of the mechanism of action.  As a result of FXa inhibition, apixaban prolongs clotting tests eg, prothrombin time, INR and activated partial thromboplastin time.  Changes observed in these clotting tests at the expected therapeutic dose are small and subject to a high degree of variability.  They are not recommended to assess the pharmacodynamic effects of apixaban. Apixaban also demonstrates anti-FXa activity as evidenced by reduction in factor Xa enzyme activity in multiple commercial anti-FXa kits; however, results differ across kits.  Data from clinical trials are only available for the Rotachrom Heparin chromogenic assay and results are presented in the following text.  Anti-FXa activity exhibits a close direct linear relationship with apixaban plasma concentration, reaching maximum values at the time of apixaban peak plasma concentrations.  The relationship between apixaban plasma concentration and anti-FXa activity is linear over a wide dose range of apixaban, and precision of the Rotachrom assay is well within acceptable limits for use in a clinical laboratory.  The dose- and concentration-related changes observed following apixaban administration are more pronounced and less variable with anti-FXa activity compared with clotting tests. Predicted steady-state peak and trough anti-FXa activity with apixaban 2. 5 mg twice-daily dosing are 1. 3 IU/mL and 0. 84 IU/mL, respectively, demonstrating <1. 6-fold fluctuation in peak-to-trough anti-FXa activity over the dosing interval. Although treatment with apixaban does not require routine monitoring of exposure, the Rotachrom anti-FXa assay may be useful in exceptional situations where knowledge of apixaban exposure may help to inform clinical decisions eg, overdose and emergency surgery. Clinical Efficacy and Safety: The apixaban clinical program was designed to demonstrate the efficacy and safety of apixaban for the prevention of venous thromboembolic events in a broad range of adult patients undergoing elective hip or knee replacement.  A total of 8464 patients were randomized in 2 pivotal, double-blind, multinational studies, comparing apixaban 2. 5 mg given Oral  ly twice daily or enoxaparin 40 mg once daily.  Included in this were 1262 patients ≥75 years, 1004 patients with low body weight, 1495 patients with BMI ≥33 kg/m2, and 415 patients with moderate renal impairment. The ADVANCE-3 study included 5407 patients undergoing elective hip replacement, and the ADVANCE-2 study included 3057 patients undergoing elective knee replacement.  Subjects received either apixaban 2. 5 mg given Oral  ly twice daily or enoxaparin 40 mg administered SC once daily.  The 1st dose of apixaban was given 12-24 hrs post-surgery, whereas enoxaparin was started 9-15 hrs prior to surgery.  Both apixaban and enoxaparin were given for 32-38 days in the ADVANCE-3 study and for 10-14 days in the ADVANCE-2 study. Based on patient medical history in the studied population of ADVANCE-3 and ADVANCE-2, 46% had hypertension, 10% had hyperlipidemia, 9% had diabetes, and 8% had coronary artery disease. Apixaban demonstrated a statistically superior reduction in the primary endpoint, a composite of all VTE/all cause death, and in the major VTE endpoint, a composite of proximal DVT, nonfatal PE, and VTE-related death, compared to enoxaparin in both elective hip or knee replacement surgery. The safety endpoints of major bleeding, the composite of major and clinically relevant non-major bleeding, and all bleeding showed similar rates for patients treated with apixaban 2. 5 mg compared with enoxaparin 40 mg.  All the bleeding criteria included surgical site bleeding. The overall incidences of adverse reactions of bleeding, anaemia and abnormalities of transaminases were numerically lower in patients on apixaban compared to enoxaparin in the phase II and phase III studies in elective hip and knee replacement surgery. In the knee replacement surgery study during the intended treatment period, 4 cases of PE were diagnosed in the apixaban arm against no cases in the enoxaparin arm.  No explanation can be given to this higher number of PE.

Pharmacokinetics

Absorption: The absolute bioavailability of apixaban is approximately 50% for doses up to 10 mg.  Apixaban is rapidly absorbed with maximum concentrations appearing 3-4 hrs after tablet intake.  Intake with food does not affect apixaban AUC or Cmax at the 10-mg dose.  Apixaban can be taken with or without food. Apixaban demonstrates linear pharmacokinetics with dose-proportional increases in exposure for Oral   doses up to 10 mg.  At doses ≥25 mg, apixaban displays dissolution-limited absorption with decreased bioavailability.  Apixaban exposure parameters exhibit low to moderate variability reflected by a within-subject and intersubject variability of approximately 20% CV and approximately 30% CV, respectively.  Distribution: Plasma protein-binding in humans is approximately 87%.  The volume of distribution is approximately 21 L. Biotransformation and Elimination: Apixaban has multiple routes of elimination.  Of the administered apixaban dose in humans, approximately 25% was recovered as metabolites, with the majority recovered in faeces.  Renal excretion of apixaban accounts for approximately 27% of total clearance.  Additional contributions from biliary and direct intestinal excretion were observed in clinical and nonclinical studies, respectively. Apixaban has a total clearance of about 3. 3 L/hr and a half-life of approximately 12 hrs.  O-demethylation and hydroxylation at the 3-oxopiperidinyl moiety are the major sites of biotransformation.  Apixaban is metabolized mainly via CYP3A4/5 with minor contributions from CYP1A2, 2C8, 2C9, 2C19, and 2J2.  Unchanged apixaban is the major drug-related component in human plasma with no active circulating metabolites present.  Apixaban is a substrate of transport proteins, P-gp and breast cancer resistance protein. Renal Impairment: There was no impact of impaired renal function on peak concentration of apixaban.  There was an increase in apixaban exposure correlated to decrease in renal function, as assessed via measured creatinine clearance.  In individuals with mild, moderate and severe renal impairment, apixaban plasma concentrations were increased 16%, 29%, and 44%, respectively, compared to individuals with normal creatinine clearance.  Renal impairment had no evident effect on the relationship between apixaban plasma concentration and anti-FXa activity. Hepatic Impairment: In a study comparing 8 subjects with mild hepatic impairment, Child-Pugh A score 5 and score 6, and 8 subjects with moderate hepatic impairment, Child-Pugh B score 7 and score 8, to 16 healthy control subjects, the single-dose pharmacokinetics and pharmacodynamics of apixaban 5 mg were not altered in subjects with hepatic impairment.  Changes in anti-Factor Xa activity and INR were comparable between subjects with mild to moderate hepatic impairment and healthy subjects. Elderly: Elderly patients exhibited higher plasma concentrations than younger patients, with mean AUC values being approximately 32% higher. Gender: Exposure to apixaban was approximately 18% higher in females than in males. Ethnic Origin and Race: The results across phase 1 studies showed no discernible difference in apixaban pharmacokinetics between White/Caucasian, Asian and Black/African-American subjects.  Findings from a population pharmacokinetic analysis in patients who received apixaban following elective hip or knee replacement surgery were consistent with the phase 1 results. Body Weight: Compared to apixaban exposure in subjects with body weight of 65-85 kg, body weight >120 kg was associated with approximately 30% lower exposure and body weight <50 kg was associated with approximately 30% higher exposure. Pharmacokinetic/Pharmacodynamic Relationship: The pharmacokinetic/pharmacodynamic relationship between apixaban plasma concentration and several PD endpoints has been evaluated after administration of a wide range of doses.  The relationship between apixaban plasma concentration and anti-factor Xa activity was best described by a linear model.  The PK/PD relationship observed in patients who received apixaban following elective hip or knee replacement surgery was consistent with that established in healthy subjects. Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic potential, fertility and embryofoetal development.  In the offspring of pregnant rats treated with apixaban, there were decreases in mating and fertility.  These effects were minimal and observed only at exposures considered sufficiently in excess of the maximum human exposure, indicating little relevance to clinical use. The major observed effects in the repeated-dose toxicity studies were those related to the pharmacodynamic action of apixaban on blood coagulation parameters.  In the toxicity studies, little to no increase of bleeding tendency was found.  However, since this may be due to a lower sensitivity of the nonclinical species compared to humans, this result should be interpreted with caution when extrapolating to humans.

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IMPORTANT WARNING:

You are at a higher risk of having a stroke after you stop taking apixaban. Do not stop taking apixaban without talking to your doctor. Continue to take apixaban even if you feel well. Be sure to refill your prescription before you run out of medication so that you will not miss any doses of apixaban. If you need to stop taking apixaban, your doctor may prescribe another anticoagulant ('blood thinner') to help prevent a blood clot from forming and causing you to have a stroke.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with apixaban and each time you refill your prescription. Read the information carefully and ask your doctor if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide. Talk to your doctor about the risks of taking apixaban.

 

Why is Apixaban prescribed?

Apixaban is used help prevent strokes or blood clots in people who have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body and possibly causing strokes) that is not caused by heart valve disease. Apixaban is in a class of medications called factor Xa inhibitors. It works by blocking the action of a certain natural substance that helps blood clots to form.

How should Apixaban be used?

Apixaban comes as a tablet to take by mouth. It is usually taken with or without food twice a day. Take apixaban at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take apixaban exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

What special precautions should I follow?

Before taking Apixaban,

  • tell your doctor and pharmacist if you are allergic to apixaban, any other medications, or any of the ingredients in apixaban tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: anticoagulants ('blood thinners') such as argatroban, dabigatran, dalteparin, desirudin, enoxaparin, fondaparinux, heparin, rivaroxaban, and warfarin; antiplatelet medications such as anagrelide,cilostazol, clopidogrel, dipyridamole , prasugrel, ticagrelor, and ticlopidine; aspirin; carbamazepine (Tegretol); clarithromycin; itraconazole; ketoconazole (Nizoral); any medications to treat or prevent blood clots; phenytoin; rifampin; ritonavir; selective serotonin reuptake inhibitors (SSRIs) such as citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; and serotonin and norepinephrine reuptake inhibitors (SNRIs) such as duloxetine, desvenlafaxine, milnacipran , and venlafaxine. Also tell your doctor if you regularly take nonsteroidal anti-inflammatory medications (NSAIDS) such as ibuprofen and naproxen. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with apixaban, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
  • tell your doctor what herbal products you are taking, especially St. Johns wort.
  • you should know that apixaban may interact with certain medications that may be used to treat you if you have a stroke or other medical emergency. In case of an emergency, you or a family member should tell the doctor or emergency room staff who treat you that you are taking apixaban.
  • tell your doctor if you have an artificial heart valve or if you have heavy bleeding anywhere in your body that cannot be stopped. Your doctor will probably tell you not to take apixaban.
  • tell your doctor if you are 80 years of age or older or if you weigh 132 pounds (60 kilograms) or less and if you have or have ever had any type of bleeding problemor kidney or liver disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking apixaban, call your doctor.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking apixaban. Your doctor may tell you to stop taking apixaban before the surgery or procedure. If you need to stop taking apixaban because you are having surgery, your doctor may prescribe a different medication to prevent blood clots during this time. Your doctor will tell you when you should start taking apixaban again after your surgery. Follow these directions carefully.
  • Call your doctor right away if you fall or injure yourself, especially if you hit your head. Your doctor may need to check you.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can Apixaban cause?

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:

  • bleeding gums

  • nosebleeds

  • heavy vaginal bleeding

  • red, pink, or brown urine

  • red or black, tarry stools

  • coughing up or vomiting blood or material that looks like coffee grounds

  • swelling or joint pain

  • headache

  • rash

  • chest pain or tightness

  • swelling of the face or tongue

  • trouble breathing

  • wheezing

  • feeling dizzy or faint

Apixaban prevents blood from clotting normally, so it may take longer than usual for you to stop bleeding if you are cut or injured. Apixaban may also cause you to bruise or bleed more easily. Call your doctor right away if bleeding or bruising is unusual, severe, or cannot be controlled.

Apixaban may cause other side effects. Call your doctor if you have any unusual problems while taking Apixaban.

In case of emergency/overdose

In case of overdose, call your Doctor. If the victim has collapsed or is not breathing, immediately consult your local medical emergency services.

Symptoms of overdose may include:

  • unusual bleeding or bruising

  • red, brown, or pink urine

  • red or black, tarry stools

  • coughing up or vomiting blood or material that looks like coffee grounds

 Ref: MedlinePlus, U.S. Natl. Library of Medicine

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