Xaliquis

Apixaban.

Each film-coated tablet contains 2.5 mg and 5.0 mg apixaban, respectively.
2.5 mg: yellow, round-shaped biconvex tablet with IMD emboss on the top side and break line on the bottom side.
5 mg: pink, round-shaped biconvex tablet with IMD emboss on the top side and break line on the bottom side.
Excipients/Inactive Ingredients: Core tablet: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, povidone k-30, sodium lauryl sulfate, magnesium stearate.
Coating material: coating agent (hypromellose, titanium dioxide, polyethylene glycol 400, talc), yellow iron oxide (Xaliquis 2.5), red iron oxide (Xaliquis 5), purified water.

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.

Prevention of VTE: elective hip or knee replacement surgery: Prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery.
Prevention of stroke: non-valvular atrial fibrillation: XALIQUIS is indicated to reduce the risk of stroke in patients with non-valvular atrial fibrillation with one or more risk factors, including patients unsuitable for warfarin/Vitamin K antagonist therapy (VKA).
Treatment of VTE: XALIQUIS is indicated for: Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE); Prevention of recurrent DVT and PE.

XALIQUIS can be taken with or without food.
if a dose is missed, the patient should take XALIQUIS immediately and then continue with twice daily intake as before.
Posology: Prevention of VTE: elective hip or knee replacement surgery: The recommended dose of Xaliquis is 2.5 mg taken orally twice daily. The initial dose should be taken 12 to 24 hours after surgery.
In patients undergoing hip replacement surgery, the recommended duration of treatment is 32 to 38 days.
In patients undergoing knee replacement surgery, the recommended duration of treatment is 10 to 14 days.
Prevention of stroke in patients with NVAF: The recommended dose of XALIQUIS is 5 mg taken orally twice daily.
Dose reduction: The recommended dose of XALIQUIS is 2.5 mg taken orally twice daily in patients with NVAF and at least two of the following characteristics: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 micromole/L).
Therapy should be continued long-term.
Treatment of DVT and PE: The recommended dose of XALIQUIS is 10 mg (2 x 5 mg) taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily for a maximum of 6 months.
Prevention of recurrent DVT and PE: The recommended dose of XALIQUIS is 2.5 mg taken orally twice daily. When prevention of recurrent DVT and PE is indicated, the 2.5 mg twice daily dose should be initiated following completion of 6 months of treatment for DVT or PE. The maximum duration of prevention of recurrent DVT and/or PE is 12 months.
Renal impairment: Prevention of VTE: elective hip or knee replacement surgery: No dose adjustment is necessary in patients with mild, moderate or severe (creatinine clearance 15-29 mL/min) renal impairment (see Pharmacology: Pharmacodynamics under Actions). Because there is limited clinical experience in patients with creatinine clearance <15 mL/min and no data in patients undergoing dialysis, apixaban is not recommended in these patients.
Prevention of stroke: NVAF: No dose adjustment is necessary in patients with mild or moderate renal impairment (see Pharmacology: Pharmacodynamics under Actions).
In patients with severe renal impairment (creatinine clearance 15-29 mL/min) the following recommendations apply (see Precautions and Pharmacology: Pharmacodynamics under Actions): Patients should receive the lower dose of apixaban 2.5 mg twice daily.
Patients with serum creatinine ≥1.5 mg/dL (133 micromole/L) associated with age ≥80 years or body weight ≤60 kg should also receive the lower dose of apixaban 2.5 mg twice daily.
In patients with creatinine clearance <15 mL/min, or in patients undergoing dialysis, there is no clinical experience therefore, apixaban is not recommended (see Precautions and Pharmacology: Pharmacodynamics under Actions).
Treatment of VTE: No dose adjustment is necessary in patients with mild, moderate, or severe (creatinine clearance 15-29 mL/min) renal impairment (see Pharmacology: Pharmacodynamics under Actions). Because there is limited clinical experience in patients with creatinine clearance <15 mL/min and no data in patients undergoing dialysis, apixaban is not recommended in these patients.
Hepatic impairment: No dose adjustment is required in patients with mild or moderate hepatic impairment.
XALIQUIS is not recommended in patients with severe hepatic impairment.
Body weight: Prevention of VTE: elective hip or knee replacement surgery: No dose adjustment required.
Treatment of VTE: No dose adjustment required.
Prevention of stroke: NVAF: No dose adjustment required, unless criteria for dose reduction are met (see Dose reduction as previously mentioned).
Gender: No dose adjustment required.
Paediatric and adolescent: The safety and efficacy of XALIQUIS in children below age 18 have not yet been established. No data are available.
Elderly: Prevention of VTE: elective hip or knee replacement surgery: No dose adjustment required.
Prevention of stroke NVAF: No dose adjustment required, unless criteria for dose reduction are met (see Dose reduction as previously mentioned).
Cardioversion (NVAF): XALIQUIS can be initiated or continued in NVAF patients who may require cardioversion.
For patients not previously treated with anticoagulants, at least 5 doses of Apixaban 5 mg twice daily [2.5 mg twice daily in patients who qualify for a dose reduction (see as previously mentioned)] should be given before cardioversion to ensure adequate anticoagulation (see Pharmacology: Pharmacodynamics under Actions).
If cardioversion is required before 5 doses of Apixaban can be administered, a 10 mg loading dose should be given, followed by 5 mg twice daily. The dosing regimen should be reduced to a 5 mg loading dose followed by 2.5 mg twice daily if the patient meets the criteria for dose reduction (see as previously mentioned). The administration of the loading dose should be given at least 2 hours before cardioversion (see Pharmacology: Pharmacodynamics under Actions).
Confirmation should be sought prior to cardioversion that the patient has taken Apixaban as prescribed. Decisions on initiation and duration of treatment should take established guideline recommendations for anticoagulant treatment in patients undergoing cardioversion into account.
Treatment of VTE: No dose adjustment required.
Converting from or to parental anticoagulants: In general, switching treatment from parenteral anticoagulants to XALIQUIS (and vice versa) can be done at the next scheduled dose.
Converting from or to warfarin or other vitamin K antagonists (VKA): When converting patients from warfarin or other VKA therapy to XALIQUIS, discontinue warfarin or other VKA therapy and start XALIQUIS when the international normalized ratio (INR) is below 2.0.
When converting from XALIQUIS to warfarin or other VKA therapy, continue XALIQUIS for 48 hours after the first dose of warfarin or other VKA therapy.
Surgery and invasive procedures: XALIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. XALIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. If surgery or invasive procedures cannot be delayed, exercise appropriate caution taking into consideration an increased risk of bleeding. This risk of bleeding should be weighed against the urgency of intervention. In non-valvular atrial fibrillation patients, bridging anticoagulation during the 24 to 48 hours after stopping XALIQUIS and prior to the intervention is not generally required. XALIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established.
Patients can continue taking XALIQUIS while being cardioverted.
For patients who are unable to swallow whole tablets, XALIQUIS tablets may be crushed and suspended in water and promptly administered orally. Alternatively, XALIQUIS tablets may be crushed and suspended in 60 mL of water promptly delivered through a nasogastric tube (see Pharmacology: Pharmacodynamics under Actions).

There is no antidote to XALIQUIS. Overdose of XALIQUIS 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, e.g., surgical haemostasis or the transfusion of fresh frozen plasma should be considered.
Administration of activated charcoal 2 and 6 hours after ingestion of a 20-mg dose of apixaban reduced mean apixaban AUC by 50% and 27%, respectively, and had no impact on C_max. Mean half-life of apixaban decreased from 13.4 hours when apixaban was administered alone to 5.3 hours and 4.9 hours, respectively, when activated charcoal was administered 2 and 6 hours after apixaban. Thus, administration of activated charcoal may be useful in the management of apixaban overdose or accidental ingestion.
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.
Depending on local availability, a consultation of a coagulation expert should be considered in case of major bleedings.

Hypersensitivity to the active substance or to any of the excipients.
Clinically significant active bleeding.
Hepatic disease associated with coagulopathy and clinically relevant bleeding risk (see Pharmacology: Pharmacodynamics under Actions).
Lesion or condition if considered a significant risk factor for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.
Concomitant treatment with any other anticoagulant agent e.g., unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, rivaroxaban, dabigatran, etc.) except under specific circumstances of switching anticoagulant therapy (see Dosage & Administration) or when UFH is given at doses necessary to maintain an open central venous or arterial catheter (see Interactions).

Haemorrhage risk: As with other anticoagulants, patients taking XALIQUIS are to be carefully observed for signs of bleeding.
XALIQUIS is recommended to be used with caution in conditions with increased risk of haemorrhage, such as: 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. XALIQUIS administration should be discontinued if severe haemorrhage occurs (see Overdosage).
Although treatment with Apixaban does not require routine monitoring of exposure, a calibrated quantitative anti-Factor Xa assay may be useful in exceptional situations where knowledge of apixaban exposure may help to inform clinical decisions, e.g., overdose and emergency surgery (see Pharmacology: Pharmacodynamics under Actions).
In the event of hemorrhagic complications, treatment must be discontinued and the source of bleeding investigated. The initiation of appropriate treatment, e.g., surgical hemostasis or the transfusion of fresh frozen plasma, should be considered. If life-threatening bleeding cannot be controlled by the previously mentioned measures, administration of prothrombin complex concentrates (PCCs) or recombinant factor VIIa may be considered. Reversal of XALIQUIS pharmacodynamic effects, as demonstrated by changes in the thrombin generation assay, has been demonstrated after administration of 4-factor PCCs in healthy subjects. However, there is no clinical experience with the use of 4-factor PCC products to reverse bleeding in individuals who have received XALIQUIS. Currently, there is no experience with the use of recombinant factor VIIa in individuals receiving apixaban.
Temporary discontinuation of XALIQUIS: Discontinuing anticoagulants, including XALIQUIS, for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of thrombosis. Avoid lapses in therapy, and if anticoagulation with XALIQUIS must be temporarily discontinued for any reason, restart therapy as soon as possible.
Renal impairment: Prevention of VTE: elective hip or knee replacement surgery.
Because there is limited clinical experience in patients with creatinine clearance <15 mL/min, apixaban is not recommended in these patients (see Pharmacology: Pharmacodynamics under Actions).
Treatment of VTE: Because there is limited clinical experience in patients with creatinine clearance <15 mL/min and no data in patients undergoing dialysis, apixaban is not recommended in these patients (see Pharmacology: Pharmacodynamics under Actions).
Prevention of stroke: NVAF: Patients with severe renal impairment (creatinine clearance 15-29 mL/min), and patients with serum creatinine ≥1.5 mg/dL (133 micromole/L) associated with age ≥80 years or body weight ≤60 kg should receive the lower dose of apixaban 2.5 mg twice daily (see Dosage & Administration).
In patients with creatinine clearance <15 mL/min, or in patients undergoing dialysis, there is no clinical experience therefore, apixaban is not recommended (see Dosage & Administration and Pharmacology: Pharmacodynamics under Actions).
Body weight: Low body weight (<60 kg) may increase haemorrhagic risk (see Pharmacology: Pharmacodynamics under Actions).
Hepatic impairment: XALIQUIS is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk (see Contraindications).
XALIQUIS is not recommended in patients with severe hepatic impairment (see Pharmacology: Pharmacodynamics under Actions).
XALIQUIS may be used with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B) (see Pharmacology: Pharmacodynamics under Actions).
Interaction with strong inhibitors of both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp): The use of XALIQUIS is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp, such as azole-antimycotics (e.g., ketoconazole, itraconazole, voriconazole and posaconazole) and HIV protease inhibitors (e.g., ritonavir). These medicinal products may increase apixaban exposure by 2-fold (see Interactions), or greater in the presence of additional factors that increase apixaban exposure (e.g., severe renal impairment).
Interaction with strong inducers of both CYP3A4 and P-gp: The concomitant use of XALIQUIS with strong CYP3A4 and P-gp inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital or St. John's Wort) may lead to a ~50% reduction in apixaban exposure. In a clinical study in atrial fibrillation patients, diminished efficacy and a higher risk of bleeding were observed with co-administration of apixaban with strong inducers of both CYP3A4 and P-gp compared with using apixaban alone. In patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp the following recommendations apply (see Interactions): for the prevention of VTE in elective hip or knee replacement surgery, for the prevention of stroke in patients with NVAF and for the prevention of recurrent DVT and PE, apixaban should be used with caution; for the treatment of DVT and treatment of PE, apixaban should not be used since efficacy may be compromised.
For the treatment of DVT or PE, XALIQUIS is not recommended in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp (see Interactions). For prevention of recurrent DVT and PE, use caution when co-administering XALIQUIS with strong inducers of both CYP3A4 and P-gp (see Interactions).
Interaction with other medicinal products affecting haemostasis: Care is to be taken if patients are treated concomitantly with medicinal products affecting haemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, platelet aggregation inhibitors or other antithrombotic agents (see Interactions).
In patients with atrial fibrillation and conditions that warrant mono or dual antiplatelet therapy, a careful assessment of the potential benefits against the potential risks should be made before combining this therapy with XALIQUIS.
Concomitant use of ASA increased the major bleeding risk on apixaban in patients with atrial fibrillation.
Spinal/epidural anaesthesia or puncture: When neuraxial anaesthesia (spinal/epidural 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 postoperative 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 hours prior to the first dose of XALIQUIS. 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 (e.g., numbness or weakness of the legs, bowel or bladder dysfunction). 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 of such need and based on pharmacokinetic data, a time interval of 20-30 hours (i.e., twice the half-life) between the last dose of apixaban and catheter withdrawal should elapse, and at least one dose should be omitted before catheter withdrawal. The next dose of apixaban may be given at least 5 hours 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, XALIQUIS is not recommended in these patients.
Patients with prosthetic heart valves: Safety and efficacy of XALIQUIS have not been studied in patients with prosthetic heart valves, with or without atrial fibrillation. Therefore, the use of XALIQUIS is not recommended in this setting.
Information about excipients: XALIQUIS contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Acute PE in hemodynamically unstable patients or patients who require thrombolysis or pulmonary embolectomy: Treatment of VTE: Initiation of XALIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy.
Patients with active cancer: Patients with active cancer can be at high risk of both venous thromboembolism and bleeding events. When apixaban is considered for DVT or PE treatment in cancer patients, a careful assesment of the benefits against the risks should be made (see also Contraindications).
Patients with antiphospholipid syndrome: Direct acting oral anticoagulants (DOACs), including XALIQUIS, are not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome (APS). In particular for patients who are triple positive (for lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2-glycoprotein I antibodies), treatment with DOACs could be associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy. The efficacy and safety of XALIQUIS in patients with APS have not been established.
Effects on ability to drive and use machines: XALIQUIS has no or negligible influence on the ability to drive and use machines.
Use in the Elderly: Increasing age may increase haemorrhagic risk (see Pharmacology: Pharmacodynamics under Actions).
Also, the co-administration of XALIQUIS with ASA in elderly patients should be used cautiously because of a potentially higher bleeding risk.

Pregnancy: There are limited 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.
Breast-feeding: It is unknown whether apixaban or its metabolites are excreted in human milk. Available data in animals have shown excretion of apixaban in milk. A risk to newborns and infants cannot be excluded.
A decision must be made to either discontinue breast-feeding or to discontinue/abstain from apixaban therapy.
Fertility: Studies in animals dosed directly with apixaban have shown no effect on fertility.

Treatment-emergent adverse reactions in post-surgery orthopedic patients: Blood and lymphatic system disorders: anemia (including postoperative and hemorrhagic anemia, and respective laboratory parameters), thrombocytopenia (including platelet count decreases).
Immune system disorders: hypersensitivity.
Eye disorders: ocular hemorrhage (including conjunctival hemorrhage).
Vascular disorders: hemorrhage (including hematoma, and vaginal and urethral hemorrhage), hypotension (including procedural hypotension).
Respiratory, thoracic and mediastinal disorders: epistaxis, hemoptysis.
Gastrointestinal disorders: nausea, gastrointestinal hemorrhage (including hematemesis and melaena), haematochezia, rectal hemorrhage, gingival bleeding.
Hepatobiliary disorders: transaminases increased (including alanine aminotransferase increased and alanine aminotransferase abnormal), aspartate aminotransferase increased gammaglutamyltransferase increased, liver function test abnormal, blood alkaline phosphatase increased, blood bilirubin increased.
Musculoskeletal and connective tissue disorders: muscle hemorrhage.
Renal and urinary disorders: hematuria (including respective laboratory parameters).
Injury, poisoning and procedural complications: contusion, post procedural hemorrhage (including post procedural hematoma, wound hemorrhage, vessel puncture site hematoma and catheter site hemorrhage), wound secretion, incision site hemorrhage (including incision site hematoma), operative hemorrhage.
Prevention of stroke and systemic embolism: NVAF: Treatment-emergent adverse reactions in NVAF patients: Immune system disorders: hypersensitivity (including drug hypersensitivity such as skin rash and anaphylactic reaction such as allergic edema).
Nervous system disorders: brain haemorrhage, other intracranial or intraspinal haemorrhage (including subdural haematoma, subarachnoid haemorrhage, and spinal haematoma).
Eye disorders: eye haemorrhage (including conjunctival haemorrhage).
Vascular disorders: other haemorrhage, haematoma, intra-abdominal haemorrhage.
Respiratory, thoracic and mediastinal disorders: epistaxis, haemoptysis, respiratory tract haemorrhage (including pulmonary alveolar haemorrhage, laryngeal haemorrhage, and pharyngeal haemorrhage).
Gastrointestinal disorders: gastrointestinal haemorrhage (including hematemesis and melaena), rectal haemorrhage, gingival bleeding, haemorrhoidal haemorrhage, haematochezia, mouth haemorrhage, retroperitoneal haemorrhage.
Renal and urinary disorders: haematuria.
Reproductive system and breast disorders: abnormal vaginal haemorrhage, urogenital haemorrhage.
General disorders and administration site conditions: application site bleeding.
Investigations: occult blood positive.
Injury, poisoning and procedural complications: contusion, traumatic haemorrhage, post procedural haemorrhage, incision site haemorrhage.
Treatment of VTE: Treatment-emergent adverse reactions in VTEtx patients: Blood and lymphatic system disorders: haemorrhagic anaemia, haemorrhagic diathesis, spontaneous haematoma.
Nervous system disorders: cerebral haemorrhage, haemorrhagic stroke.
Eye disorders: conjunctival haemorrhage, eye haemorrhage, retinal haemorrhage, schlera haemorrhage, vitreous haemorrhage.
Ear and labyrinth disorders: ear haemorrhage.
Cardiac disorders: pericardial haemorrhage.
Vascular disorders: haematoma, haemorrhage, intra-abdominal haematoma, shock haemorrhagic.
Respiratory, thoracic, and mediastinal disorders: epistaxis, haemoptysis, pulmonary alveolar haemorrhage.
Gastrointestinal disorders: gingival bleeding, rectal haemorrhage, haematochezia, haemorrhoidal, haemorrhage, gastrointestinal haemorrhage, haematemesis, melaena, anal haemorrhage, gastric ulcer haemorrhage, mouth haemorrhage, abdominal wall haematoma, Mallory-Weiss syndrome, gastric haemorrhage, peptic ulcer haemorrhage, small intestine haemorrhage.
Skin and subcutaneous tissue disorders: ecchymosis, skin haemorrhage, petechiae purpura, increased tendency to bleed, blood blister, skin ulcer haemorrhage.
Musculoskeletal and connective tissue disorders: muscle haemorrhage.
Renal and urinary disorders: haematuria, haemorrhage urinary tract.
Reproductive system and breast disorders: menorrhagia, vaginal haemorrhage, metrorrhagia, menometrorrhagia, uterine haemorrhage, genital haemorrhage, breast haematoma, haematospermia, postmenopausal haemorrhage.
General disorders and administration site conditions: injection site haematoma, vessel puncture site haematoma, injection site haemorrhage, infusion site haematoma.
Investigations: blood urine present, occult blood positive, occult blood, red blood cells urine positive.
Injury, poisoning, and procedural complications: contusion, wound haemorrhage, post procedural haemorrhage, traumatic haematoma, periorbital haematoma, vascular pseudoaneurysm, subcutaneous haematoma, procedural haematoma, post procedural haematoma, post procedural haematuria, extradural haematoma, renal haematoma, subdural haemorrhage

Effect of other drugs on apixaban: Inhibitors of CYP3A4 and P-gp: Co-administration of apixaban with ketoconazole (400 mg once a day), 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 C_max. No dose adjustment for apixaban is required with concomitant ketoconazole therapy, however apixaban should be used with caution in patients receiving concomitant systemic treatment with azole-antimycotics such as ketoconazole or other strong inhibitors of both CYP3A4 and P-gp (see Precautions).
Active substances that are not considered strong inhibitors of both CYP3A4 and P-gp (e.g., diltiazem, naproxen, clarithromycin, amiodarone, verapamil, quinidine) are expected to increase apixaban plasma concentrations to a lesser extent. No dose adjustment for apixaban is required when co-administered with agents that are not strong inhibitors of both CYP3A4 and P-gp.
Inducers of CYP3A4 and P-gp: Co-administration of apixaban with rifampin, a strong inducer of both CYP3A4 and P-gp, led to an approximate 54% and 42% decrease in mean apixaban AUC and C_max, respectively. The concomitant use of apixaban with other strong CYP3A4 and P-gp inducers (e.g., phenytoin, carbamazepine, phenobarbital or St. John's Wort) may also lead to reduced apixaban plasma concentrations. No dose adjustment for apixaban is required during concomitant therapy with such medicinal products, however in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp apixaban should be used with caution for the prevention of VTE in elective hip or knee replacement surgery, for the prevention of stroke in patients with NVAF and for the prevention of recurrent DVT and PE.
Apixaban is not recommended for the treatment of DVT and PE in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp since efficacy may be compromised.
Anticoagulants: After combined administration of enoxaparin (40 mg single dose) with apixaban (5 mg single dose), 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 (see Precautions).
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 (75 mg once a day) or with the combination of clopidogrel 75 mg and acetylsalicylic acid 162 mg once daily did not show a relevant increase in bleeding time, platelet aggregation, or clotting tests (PT, INR, and aPTT) compared to administration of the antiplatelet agents without apixaban.
Naproxen (500 mg), an inhibitor of P-gp, led to a 1.5-fold and 1.6-fold increase in mean apixaban AUC and C_max, 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. Care is to be taken if patients are treated concomitantly with NSAIDs (including acetylsalicylic acid) and/or platelet aggregation inhibitors because these medicinal products typically increase the bleeding risk (see Precautions).
Agents associated with serious bleeding are not recommended concomitantly with XALIQUIS, such as: thrombolytic agents, GPIIb/IIIa receptor antagonists, thienopyridines (e.g., clopidogrel), dipyridamole, dextran and sulfinpyrazone.
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 two drugs together, mean apixaban AUC and C_max 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 C_max.
Laboratory parameters: Clotting tests (e.g., PT, INR, and aPTT) 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 (see Pharmacology: Pharmacodynamics under Actions).
Paediatric population: Interaction studies have only been performed in adults.
Effect of apixaban on other drugs: In vitro apixaban studies showed no inhibitory effect on the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (IC50>45 μM) and weak inhibitory effect on the activity of CYP2C19 (IC50>20 μM) at the 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 μM. 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 as follows, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, or atenolol.
Digoxin: Co-administration of apixaban (20 mg once a day) and digoxin (0.25 mg once a day), a P-gp substrate, did not affect digoxin AUC or C_max. Therefore, apixaban does not inhibit P-gp mediated substrate transport.
Naproxen: Co-administration of single doses of apixaban (10 mg) and naproxen (500 mg), a commonly used NSAID, did not have any effect on the naproxen AUC or C_max.
Atenolol: Co-administration of a single dose of apixaban (10 mg) and atenolol (100 mg), a common beta-blocker, did not alter the pharmacokinetics of atenolol.
Activated charcoal: Administration of activated charcoal reduces apixaban exposure (see Overdosage).

Store below 30°C, and protect from direct sunlight.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

B01AF02 - apixaban ; Belongs to the class of direct factor Xa inhibitors. Used in the treatment of thrombosis.

K