apixaban, Eliquis

 Indications

Decreases risk of stroke/systemic embolism associated

with nonvalvular atrial fibrillation. Prevention of deep

vein thrombosis that may lead to pulmonary embolism

following knee or hip replacement surgery. Treatment

of and reduction in risk of recurrence of deep vein

thrombosis (DVT) or pulmonary embolism (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 thrombininduced

platelet aggregation. Decreases thrombin generation

and thrombus development. Therapeutic

Effects: Treatment and prevention of thromboembolic

events.

Pharmacokinetics

Absorption: 50% absorbed following oral administration.

Distribution: Unknown.

Metabolism and Excretion: 25% metabolized

(mostly by CYP3A4) and 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 A

hemostasis)

ROUTE ONSET PEAK DURATION

PO unknown 3–4 hr† 24 hr

†Blood levels.

Contraindications/Precautions

Contraindicated in: Previous severe hypersensitivity

reactions; Active pathological bleeding; Severe hepatic

impairment; Not recommended for use in patients

with prosthetic heart valves; Concurrent use of strong

dual inducers of CYP3A4 and P-gp; PE with hemodynamic

instability or requiring thrombolysis or pulmonary

embolectomy; Lactation: Should not be used.

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 (qrisk of spinal hematoma); Discontinuation

qrisk of thromboses; Surgery; Renal impairment (dose

pmay be required; Moderate hepatic impairment (q

risk of bleeding); Concurrent use of strong dual inhibitors

of CYP3A4 and P-gp systems (doseprequired);

OB: Use during pregnancy only if potential benefit outweighs

possible risks to mother and fetus; Pedi: Safety

and effectiveness not established.

Adverse Reactions/Side Effects

Hemat: BLEEDING. Misc: hypersensitivity reactions including

ANAPHYLAXIS.

Interactions

Drug-Drug:qrisk of bleeding with other anticoagulants,

aspirin, clopidogrel, ticagrelor, prasugrel,

fibrinolytics, NSAIDs, SNRIs, or SSRIs. Concurrent

use of strong inhibitors of both the CYP3A4 and

P-gp enzyme systems (including clarithromycin, itraconazole,

ketoconazole, and ritonavir)qlevels

and bleeding risk; dosage of apixaban should bepto

2.5 mg twice daily. If other reasons forpdose exist,

apixaban should be avoided. Inducers of the CYP3A4

enzyme system and the P-gp system including carbamazepine,

phenytoin, rifampin willplevels and

mayqrisk 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 canplevels andqrisk 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): HD—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

post-operatively (when hemostasis is achieved) continued

for 35 days after hip replacement or 12 days after

knee replacement.

Treatment of DVT or PE

PO (Adults): 10 mg twice daily for 7 days, then 5 mg

twice daily.

Reduction in Risk of Recurrence of DVT or

PE

PO (Adults): 2.5 mg twice daily after 6 mo of treatment

of DVT or PE.

Availability

Tablets: 2.5 mg, 5 mg.