Drug information of Apixaban

Apixaban

Drug group: Anticoagulants

Apixaban is an oral, direct, and highly selective factor Xa (FXa) inhibitor (of both free and prothrombinase-bound FXa independently of antithrombin III) for the prevention and treatment of thromboembolic diseases.

Mechanism of effect

Factor Xa inhibitor that inhibits platelet activation by selectively and reversibly blocking the active site of factor Xa without requiring a cofactor (eg, antithrombin III) for activity

Inhibits free and clot-bound factor Xa, and prothrombinase activity; no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin

Blood coagulation cascade is dependent on the activation of factor X to factor Xa via the intrinsic and extrinsic pathways, which play a central role in the blood coagulation cascade

Pharmacodynamic

Apixaban acts by inhibiting coagulation, and thus prevents development of blood clots. As a result of FXa inhibition, apixaban prolongs clotting tests such as prothrombin time (PT), INR, and activated partial thromboplastin time (aPTT).

Changes observed in these clotting tests at the expected therapeutic dose, however, are small, subject to a high degree of variability, and not useful in monitoring the anticoagulation effect of apixaban..

Pharmacokinetics

  • Bioavailability: Displays prolonged absorption
  • Peak Plasma Concentration: 3-4 hr
  • Protein Bound: 87%
  • Vdss: 21 L
  • Metabolized mainly by CYP3A4,Metabolized with minor contributions from CYP1A2, 2C8, 2C9, 2C19 and 2J2.
  • Major sites of biotransformation: O-demethylation and hydroxylation at the 3-oxopirperidinyl moiety
  • Half-life: 5-6 hr (dominant); 12 hr (apparent half-life with repeated dosing)
  • Dialyzable: No
  • Renal clearance: 27%
  • Excretion: 25% in urine and feces as metabolites; renal excretion accounts for 27% of total clearance; biliary and direct intestinal excretion contributes to elimination in feces

Dosage

Adult

Stroke Prophylaxis with Atrial Fibrillation

Indicated to reduce risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation

5 mg PO BID

Postoperative Prophylaxis of DVT/PE

Indicated following hip or knee replacement surgery

Initial: Give 2.5 mg PO 12-24 hr after surgery

Duration of therapy (hip replacement): 2.5 mg PO BID for 35 days

Duration of therapy (knee replacement): 2.5 mg PO BID for 12 days

DVT or PE Treatment

10 mg PO BID x 7 days, then 5 mg BID

Reduce risk for recurrent DVT or PE

Indicated to reduce the risk of recurrent DVT and PE following initial 6 months treatment for DVT and/or PE

2.5 mg PO BID

Pediatric

Safety and efficacy not established

Alerts

Discontinuing in patients with nonvalvular atrial fibrillation

  • Premature discontinuation of any oral anticoagulant, including, apixaban, increases risk of thrombotic events; consider using another anticoagulant if anticoagulation with apixaban is discontinued for a reason other than pathological bleeding or completion of a course of therapy
  • 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

Spinal/epidural hematoma

  • Increased risk of epidural or spinal hematoma when used with neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture (can result in long-term or permanent paralysis)
  • Risk increased with indwelling epidural catheters for administration of analgesia or by the concomitant use of drugs affecting hemostasis (eg, NSAIDs, platelet aggregation inhibitors, other anticoagulants)
  • Risk also increased by traumatic or repeated epidural or spinal puncture; if this occurs, delay apixaban administration for 48 hr
  • Monitor patients for signs and symptoms of neurologic impairment; if neurologic compromise is noted, urgent treatment is necessary
  • Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hr after the last administration of apixaban; the next apixaban dose should not be administered earlier than 5 hr after the removal of the catheter

Points of recommendation

This medicine may need to be stopped before certain types of surgery as your doctor has told you. If apixaban is stopped, your doctor will tell you when to start taking apixaban again after your surgery or procedure.

Have blood work checked as you have been told by the doctor. Talk with the doctor.

Do not run out of apixaban.

You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.

If you fall or hurt yourself, or if you hit your head, call your doctor right away. Talk with your doctor even if you feel fine.

Take with or without food.

If you have trouble swallowing apixaban, it can be crushed and mixed in water, apple juice, or applesauce. If you crush and mix apixaban, take it within 4 hours of mixing.

To gain the most benefit, do not miss doses.

Keep taking apixaban as you have been told by your doctor or other health care provider, even if you feel well.

Those who have feeding tubes may use apixaban. Use as you have been told. Flush the feeding tube after apixaban is given.

Pregnancy level

B


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