General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
a-pix-a-ban

Trade Name(s)

• Eliquis

Ther. Class.

anticoagulants

Pharm. Class.

factor xa inhibitors

Indications

• Reduction in risk of stroke/systemic embolism associated with nonvalvular atrial fibrillation.
• Prevention of deep vein thrombosis (DVT) that may lead to pulmonary embolism (PE) following knee or hip replacement surgery.
• Treatment of and reduction in risk of recurrence of DVT or PE.

Action

Acts as a selective, reversible site inhibitor of factor Xa, inhibiting both free and bound factor. Does not affect platelet aggregation directly, but does inhibit thrombin-induced platelet aggregation. Decreases thrombin generation and thrombus development.

Therapeutic Effect(s):

Treatment and prevention of thromboembolic events.

Pharmacokinetics

Absorption: 50% absorbed following oral administration.

Distribution: Unknown.

Metabolism and Excretion: Primarily metabolized by the liver by the CYP3A4 isoenzyme; excreted in urine and feces. Biliary and direct intestinal excretion account for fecal elimination.

Half-life: 6 hr (12 hr after repeated dosing due to prolonged absorption).

TIME/ACTION PROFILE (effect on hemostasis)

Contraindication/Precautions

Contraindicated in:

• Previous severe hypersensitivity reactions;
• Active pathological bleeding;
• Severe hepatic impairment;
• Prosthetic heart valves;
• PE with hemodynamic instability or requiring thrombolysis or pulmonary embolectomy;
• Triple-positive antiphospholipid syndrome (↑ risk of thrombosis);
• Lactation:  Lactation.

Use Cautiously in:

• Neuroaxial spinal anesthesia or spinal puncture, especially if concurrent with an indwelling epidural catheter, drugs affecting hemostasis, history of traumatic/repeated spinal puncture or spinal deformity (↑ risk of spinal hematoma);
• Surgery;
• Renal impairment (dose ↓ may be required);
• Moderate hepatic impairment (↑ risk of bleeding);
• Rep:   Women of reproductive potential;

• OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;

  Pedi:  Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

Hemat: BLEEDING

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• ↑ risk of bleeding with other  anticoagulants,  aspirin,  clopidogrel,  ticagrelor,  prasugrel,  fibrinolytics,  NSAIDs,  SNRIs, or  SSRIs.
• Concurrent use of strong inhibitors of both CYP3A4 and P-glycoprotein (P-gp), including  itraconazole,  ketoconazole, and  ritonavir, ↑ levels and bleeding risk; may need to ↓ apixaban dose or avoid concurrent use.
• Inducers of CYP3A4 and P-gp system, including  carbamazepine,  phenytoin,  rifampin, will ↓ levels and may ↑ risk of thromboses; avoid concomitant use.

Drug-Natural Products:

Concurrent use  St. John's wort , a strong dual inducer of the CYP3A4 and P-gp enzyme systems can ↓ levels and ↑ risk of thromboses and should be avoided.

Route/Dosage

Reduction in Risk of Stroke/Systemic Embolism in Nonvalvular Atrial Fibrillation

PO (Adults): 5 mg twice daily;  Any 2 of the following: age ≥80 yr, weight ≤60 kg, serum creatinine ≥1.5 mg/dL:  2.5 mg twice daily;  Concurrent use of strong inhibitors of both CYP3A4 and P-gp:  2.5 mg twice daily; if patient already taking 2.5 mg twice daily, avoid concomitant use.

Renal Impairment 
PO (Adults): Hemodialysis:  5 mg twice daily;  HD and either age ≥80 yr or weight ≤60 kg:  2.5 mg twice daily.

Prevention of Deep Vein Thrombosis Following Knee or Hip Replacement Surgery

PO (Adults): 2.5 mg twice daily, initiated 12–24 hr postoperatively (when hemostasis is achieved) continued for 35 days after hip replacement or 12 days after knee replacement;  Concurrent use of strong inhibitors of both CYP3A4 and P-gp:  Avoid concomitant use.

Treatment of Deep Vein Thrombosis or Pulmonary Embolism

PO (Adults): 10 mg twice daily for 7 days, then 5 mg twice daily;  Concurrent use of strong inhibitors of both CYP3A4 and P-gp:  2.5 mg twice daily

Reduction in Risk of Recurrence of Deep Vein Thrombosis or Pulmonary Embolism

PO (Adults): 2.5 mg twice daily after ≥6 mo of treatment of DVT or PE;  Concurrent use of strong inhibitors of both CYP3A4 and P-gp:  Avoid concomitant use.

Availability (generic available)

Tablets: 2.5 mg, 5 mg

Assessment

• Assess patient for symptoms of stroke, DVT, PE, bleeding, or peripheral vascular disease periodically during therapy.

Antidote is andexanet alfa. Effects persist for at least 24 hrs after last dose. Oral activated charcoal decreases apixaban absorption, lowering plasma concentrations. Other agents and hemodialysis do not have a significant effect.

Implementation

• High Alert: Do not confuse apixaban with axitinib.
• When  converting from warfarin , discontinue warfarin and start apixaban when INR is <2.0.
• When  converting from apixaban to warfarin , apixaban affects INR, so INR measurements may not be useful for determining appropriate dose of warfarin. If continuous anticoagulation is necessary, discontinue apixaban and begin both a parenteral anticoagulant and warfarin at time of next dose of apixaban, discontinue parenteral anticoagulant when INR reaches acceptable range.
• When  switching between apixaban and anticoagulants other than warfarin , discontinue one being taken and begin the other at the next scheduled dose.
• For surgery , discontinue apixaban at least 48 hrs before invasive or surgical procedures with a moderate or high risk of unacceptable or clinically significant bleeding or at least 24 hrs prior to procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled.
• PO Administer twice daily without regard to food.
  • For patients who cannot swallow tablet, 5 mg and 2.5 mg tablets can be crushed, suspended in water, D5W, or apple juice, or mixed with applesauce and administered immediately orally. May also be suspended in 60 mL of water or D5W and promptly administered through a nasogastric tube.

Patient/Family Teaching

• Instruct patient to take apixaban as directed. Take missed doses as soon as remembered on the same day and resume twice daily administration; do not double doses. Do not discontinue without consulting health care professional; may increase risk of having a stroke, DVT, or PE. If temporarily discontinued, restart as soon as possible. Store apixaban at room temperature. Advise patient to read  Medication Guide  before beginning therapy and with each Rx refill in case of changes.
• Inform patient that they may bruise and bleed more easily or longer than usual. Advise patient to notify health care professional immediately if signs of bleeding (unusual bruising, pink or brown urine, red or black, tarry stools, coughing up blood, vomiting blood, pain or swelling in a joint, headache, dizziness, weakness, recurring nose bleeds, unusual bleeding from gums, heavier than normal menstrual bleeding, dyspepsia, abdominal pain, epigastric pain) occurs or if injury occurs, especially head injury.
• Caution patient to notify health care professional if skin rash or signs of severe allergic reaction (chest pain or tightness, swelling of face or tongue, trouble breathing or wheezing, feeling dizzy or faint) occur.
• Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort. Risk of bleeding is increased with aspirin, NSAIDs, warfarin, heparin, SSRIs or SNRIs.
• Inform patient having had neuraxial anesthesia or spinal puncture to watch for signs and symptoms of spinal or epidural hematomas (numbness or weakness of legs, bowel or bladder dysfunction). Notify health care professional immediately if symptoms occur.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. May increase risk of uterine bleeding in pregnant women, fetus, and neonate; advise patient to notify health care professional if significant uterine bleeding occurs.

Evaluation/Desired Outcomes

Reduction in the risk and treatment of stroke and systemic embolism.