Apixaban

Brand Names: Apixaban

Drug Class: Factor Xa Inhibitor

Overview

11 DESCRIPTION Apixaban, a factor Xa (FXa) inhibitor, is chemically described as 1-(4- methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4 c]pyridine-3-carboxamide. Its molecular formula is C 25 H 25 N 5 O 4 , which corresponds to a molecular weight of 459.5. Apixaban has the following structural formula: Apixaban is a white to off white crystalline powder.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Apixaban is a selective inhibitor of FXa. It does not require antithrombin III for antithrombotic activity. Apixaban inhibits free and clot-bound FXa, and prothrombinase activity. Apixaban has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, apixaban decreases thrombin generation and thrombus development. 12.2 Pharmacodynamics As a result of FXa inhibition, apixaban prolongs clotting tests such as prothrombin time (PT), INR, and activated partial thromboplastin time (aPTT).

Indications

  • 1 INDICATIONS & USAGE Apixaban is a factor Xa inhibitor indicated: to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. ( 1.1 ) for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. ( 1.2 ) for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. ( 1.3 , 1.4 , 1.5 ) 1.

Common Doses

  • 5 mg
  • 1.5 mg
  • 2.5 mg
  • 10 mg

Dosage

2 DOSAGE & ADMINISTRATION Reduction of risk of stroke and systemic embolism in nonvalvular atrial fibrillation: The recommended dose is 5 mg orally twice daily. ( 2.1 ) In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. ( 2.1 ) Prophylaxis of DVT following hip or knee replacement surgery: The recommended dose is 2.5 mg orally twice daily. ( 2.

Black Box Warning

BOXED WARNING WARNING: (A) PREMATURE DISCONTINUATION OF APIXABAN INCREASES THE RISK OF THROMBOTIC EVENTS (B) SPINAL/EPIDURAL HEMATOMA (A) PREMATURE DISCONTINUATION OF APIXABAN INCREASES THE RISK OF THROMBOTIC EVENTS Premature discontinuation of any oral anticoagulant, including apixaban, increases the risk of thrombotic events. If anticoagulation with apixaban is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.4), Warnings and Precautions (5.

Contraindications

  • 4 CONTRAINDICATIONS Apixaban tablets are contraindicated in patients with the following conditions: • Active pathological bleeding [see Warnings and Precautions ( 5.2 ) and Adverse Reactions( 6.1) ] • Severe hypersensitivity reaction to apixaban (e.g., anaphylactic reactions) [see Adverse Reactions ( 6.1 )] Active pathological bleeding ( 4 ) Severe hypersensitivity to apixaban ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the prescribing information. • Increased risk of thrombotic events after premature discontinuation [see Warnings and Precautions ( 5.1 )] • Bleeding [see Warnings and Precautions ( 5.2 )] • Spinal/epidural anesthesia or puncture [see Warnings and Precautions ( 5.3 )] Most common adverse reactions (>1%) are related to bleeding. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Indoco Remedies Limited at +1-855-642-2594 or FDA at 1-800-FDA-1088 or www.fda.

Interactions

  • 7 DRUG INTERACTIONS Apixaban is a substrate of both CYP3A4 and P-gp. Inhibitors of CYP3A4 and P-gp increase exposure to apixaban and increase the risk of bleeding. Inducers of CYP3A4 and P-gp decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events. Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban. Reduce apixaban dose or avoid coadministration. ( 2.5 , 7.1 , 12.3 ) Simultaneous use of combined P-gp and strong CYP3A4 inducers reduces blood levels of apixaban: Avoid concomitant use. ( 7.2 , 12.3 ) 7.