Apixa CCP

Apixaban.

2.5 mg: Light yellow, round, flat with bevel edge film-coated tablet. One side has incision, letter "A" and "P" on each side. Another side has the figure "2/5".
Each film-coated tablet contains apixaban 2.5 mg.
5 mg: Pink, oval, biconvex, one side has incision, letter "A" and "P" on each side, another side has the figure "5".
Each film-coated tablet contains apixaban 5 mg.

Pharmacology: Pharmacodynamics: Mechanism of action: Apixaban is an oral, reversible, direct and selective active site inhibitor of factor Xa (FXa). It does not require a cofactor (antithrombin III) for antithrombotic activity. Apixaban inhibits free and clot-bound FXa and prothrombinase activity, resulting in decreased thrombin generation and thrombus development.
Pharmacokinetics: Apixaban is rapid absorbed with an absolute bioavailability of about 50% and peak plasma concentrations are reached 3-4 hours after oral administration. Plasma protein binding is about 87%. Apixaban is metabolized in the liver mainly via the P450 cytochromes CYP3A4, CYP3A5 and is excreted renally and in the feces as unchanged drug and inactive metabolites. The half-life is about 12 hours.

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

Recommended Dose: Adult: Prevention of venous thromboembolic events (VTE): elective hip or knee replacement surgery: The recommended dose is 2.5 mg twice daily. The initial dose should be administered at least 12-24 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 and systemic embolism: non-valvular atrial fibrillation: The recommended dose is 5 mg twice daily.
In patients at least 2 of the following characteristics, age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL, the recommended dose is 2.5 mg twice daily.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE): The recommended dose is 10 mg twice daily for 7 days, followed by 5 mg twice daily.
Prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE): The recommended dose is 2.5 mg twice daily after at least 6 months of treatment for DVT or PE.
Renal impairment: Prevention of venous thromboembolic events (VTE): elective hip or knee replacement surgery: No dosage adjustment is necessary in patients with mild, moderate or severe (creatinine clearance 15 to 29 mL/min) renal impairment.
Prevention of stroke and systemic embolism: non-valvular atrial fibrillation: No dosage adjustment is necessary in patients with creatinine clearance 15 to 29 mL/min.
Treatment of venous thromboembolic events (VTE): No dosage adjustment is necessary in patients with mild, moderate or severe (creatinine clearance 15 to 29 mL/min) renal impairment.
Hepatic impairment: No dosage adjustment is necessary in patients with mild hepatic impairment (Child-Pugh class A). Because of limited experience, the manufacturer states that dosage recommendations cannot be provided in patients with moderate hepatic impairment (Child-Pugh class B). The use of apixaban is not recommended in patients with severe hepatic impairment (Child-Pugh class C).
Elderly: Prevention of venous thromboembolic events (VTE): elective hip or knee replacement surgery: No dose adjustment required.
Prevention of stroke and systemic embolism: non-valvular atrial fibrillation: If patient is ≥80 years of age and either weighs ≤60 kg or has a serum creatinine ≥1.5 mg/dL, then reduce dose to 2.5 mg twice daily.
Treatment of venous thromboembolic events (VTE): No dose adjustment required.
Mode of Administration: APIXA CCP is administered orally twice daily without regard to food.

Overdose and Treatment: There is no antidote to apixaban. Overdose of apixaban may result in a higher risk of bleeding. 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.

Severe hypersensitivity reaction (anaphylactic reactions) to apixaban or any component of the formulation.
Active pathological bleeding.

Bleeding risk: Apixaban increases the risk of bleeding and can cause serious, potentially fatal bleeding. Discontinue use of apixaban in patients with active pathological hemorrhage. Advise patients to be aware of the signs and symptoms of blood loss and instruct them to immediately report them or go to an emergency department.
Discontinuation: Premature discontinuation of any oral anticoagulant including apixaban, increases the risk of thrombotic events. If anticoagulation is discontinued for a reason other than pathological bleeding or completion of therapy, consider coverage with another anticoagulant.
Apixaban therapy should be temporarily interrupted prior to any elective surgery or other invasive procedure to reduce the risk of bleeding.
Apixaban is not recommended in patients with severe hepatic impairment.
Apixaban is not recommended in patients with renal impairment because there is limited clinical experience in patients with creatinine clearance ≤15 mL/min and no data in patients undergoing dialysis.

Pregnancy: Data are lacking on the use of apixaban in pregnant women. Animal studies have not demonstrated any evidence of fetotoxic effects; however, increased maternal bleeding was observed when apixaban was administered to pregnant animals at doses ranging from 1-19 times the human exposure at the maximum recommended dose.
Lactation: It is not known whether apixaban is excreted in breast milk. Apixaban is not recommended for use in breast-feeding women.

Common: Dermatologic: contusion (1.4% to 2.2%).
Gastrointestinal: bleeding gums (less than 0.1% to 1.4%).
Hematologic: hematoma (DVT 1.3% to 1.5%).
Reproductive: menorrhagia (1.4%).
Respiratory: bleeding from nose (DVT and pulmonary embolism 1.5% to 3.6%; DVT prophylaxis 0.1% to less than 1%), hemoptysis (less than 0.1% to 1.2%).
Serious: Gastrointestinal: gastrointestinal hemorrhage (atrial fibrillation 0.83%/year; DVT prophylaxis 0.1% to less than 1%; DVT and pulmonary embolism 0.1% to less than 1%), hematochezia (0.1% to less than 1%), rectal hemorrhage (less than 0.1% to 1%), upper gastrointestinal bleeding.
Hematologic: Hemorrhage (atrial fibrillation 2.08%/year; DVT prophylaxis 2.88% to 4.83%), hemorrhage (0.1% to 1.4%), hemorrhage, major (0.1% to 2.13%), hemorrhage, operative (DVT prophylaxis 0.1% to less than 1%).
Hepatic: Alkaline phosphatase raised (DVT prophylaxis 0.1% to less than 1%), liver function test abnormal (DVT prophylaxis 0.1% to less than 1%), serum bilirubin raised (DVT prophylaxis 0.1% to less than 1%).
Immunologic: hypersensitivity reaction (atrial fibrillation, less than 1%).
Musculoskeletal: hemorrhage of muscle (less than 0.1% to less than 1%).
Neurologic: extradural intracranial hematoma, intracranial hemorrhage (0.33% to 0.34% per year), non-traumatic spinal subdural hematoma, traumatic spinal subdural hematoma.
Ophthalmic: conjunctival hemorrhage (0.1% to less than 1%), retinal hemorrhage (0.1% to less than 1%).
Renal: hematuria (DVT 1.4% to 2.1%; DVT prophylaxis 0.1% to less than 1%).

Concomitant use of apixaban and diltiazem (a moderate CYP3A4 and weak P-gp inhibitor) increased AUC and peak plasma concentrations of apixaban by 1.4- and 1.3-fold, respectively.
Concomitant use of apixaban and ketoconazole (a strong inhibitor of both P-gp and CYP3A4) substantially increased the AUC and peak plasma concentration of apixaban by 2- and 1.6-fold, respectively.
Concomitant use of apixaban and naproxen (a P-gp inhibitor) increased the AUC and peak plasma concentration of apixaban by 1.5- and 1.6-fold, respectively.
Concomitant use of apixaban and rifampin (a strong inducer of both P-gp and CYP3A4) decreased AUC and peak plasma concentration of apixaban by 54 and 42%, respectively.
Concomitant use of apixaban and drugs that affect hemostasis (e.g., aspirin or other antiplatelet drugs, heparin or other anticoagulants, fibrinolytics, selective serotonin-reuptake inhibitors, selective serotonin- and norepinephrine-reuptake inhibitors, nonsteroidal anti-inflammatory agents (NSAIAs)) increases the risk of bleeding.

Store below 30°C.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

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

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