Apixaban

An oral factor Xa inhibitor.

Trade name Eliquis.

Indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Approved for treating deep vein thrombosis and pulmonary embolism and for preventing recurrent episodes of these conditions.

A selective Factor Xa inhibitor approved for preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Half-life elimination 12 hours.

Hepatic metabolism time to peak level 3-4 hours.

25% renal elimination.

Only 1/3 of this drug is eliminated by the kidneys, with the rest eliminated by the fecal route.

In the AMPLIFY study, the risk of a composite endpoint including recurrent symptomatic venous thromboembolism (VTE) or VTE-related death was reduced 16% with apixaban versus the standard regimen.

Major bleeds were reduced by two-thirds, compared to standard regimen.

Contraindicated in patients with prosthetic heart valves.

Administered in a fixed dose of 2.5 -5 mg twice daily: The 2.5 mg twice a day doses recommended for patients 80 years or older, bodyweight of 60 kg or less, serum creatinine of 1.5 mg/dL or higher. If the patient takes a strong dual inhibitors of CYP3A4 or P-gp recommended dosage 2.5 mg b.i.d.

In patients having undergone elective knee replacement surgery this drug compared to enoxaparin had better efficacy with a similar or lower risk of bleeding (Lassen MR et al).

In a randomized phase 3 controlled trial apaxiban vs injectable enoxaparin in patients undergoing elective total hip replacement resulted in a lowered rate (1.4% vs 3.9%), without increased bleeding(4.8% vs 5.0%) (Lassen MR et al).

In the above study apixaban was given 2.5 mg twice daily 12-24 hours after elective surgery and contnued for 35 days, while enoxaparin dose was 40 mg/day starting the evening before surgery (Lasen MR et al).

Reduces the incidence a venous thromboembolism in patients undergoing orthopedic surgery and prevents thromboembolic events in patients with atrial fibrillation who are not candidates for oral vitamin K antagonist therapy.

The addition of this drug 5 mg b.i.d., to standard anti-platelet therapy, either asprin or aspirin plus clopidogrel, in high risk patients after an acute coronary syndrome increased number of major bleeding events without a significant reduction in recurrent ischemic events (APPRAISE-2).

In a double-blind study, placebo-controlled acutely ill patients with CHF or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism who were hospitalized for at least three days were randomized to apixaban , 2 1/2 mg orally twice a day for 30 days, or enoxaparin 40 mg subcutaneously for 6-14 days: the no thromboembolism and death occurred in 2.71% of the patients treated with apixaban vs. 3.06% for those treated with enoxaparin, and the former drug was associated with significant more major bleeding events than enoxaparin with .47% vs. 0.19% events, respectively (ADOPT trial).

ARISTOTLE study-Apixaban versus warfarin in patients with atrial fibrillation, a randomized double-blind trial of 5 mg BID of apixaban versus warfarin and 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke:apixaban was superior to warfarin in preventing stroke or systemic embolism, cause less bleeding and resulted in less mortality.

ARISTOTLE study the rate of major bleeding was 2.13% in the apixaban group, and 3.09% per year in the warfarin group, and the rates of death from any cause were 3.52% and 3.94%, respectively.

Failed to show a benefit relative to enoxaparin (Lovenox).

In a study comparing it to warfarin in more than 18,000 patients it was superior for the primary study endpoint of reducing the risk of stroke and systemic embolism.

Superiority over warfarin primarily attributable to reduction in hemorrhagic and ischemic strokes with hemorrhagic conversion compared to warfarin.

Treatment results in significantly lower death rate of all cause death than treatment with warfarin because of reduction in cardiovascular death, particularly stroke deaths.

Clinical trials show significantly fewer major bleeding events than in patients treated with warfarin.

The rate of major bleeding events is 2.13% per year compared to 3.09% with warfarin.

With the use of this drug hemorrhagic events including hemorrhagic stroke occurs in 0.06% per year, compared to 0.24% of patients per year treated with warfarin..

In the AMPLIFY-EXT trial enrolled patients with deep vein thrombosis or pulmonary embolism who had completed 6-12 months of anticoagulant treatment and randomized to either placebo or this agent 2.5 or 5 mg twice daily for one year: Symptomatic recurrent DTE or all-cause that was lowest in patients receiving spica an 2.5 mg (3.8%), compared with apixaban 5 mg (4.2%) and placebo (11.6%), and recurrent VTE or VTE related death was 1.7% in the apixaban arms 8.8% in the placebo arm.

In the above study major bleeding occurred in 0.2% in the lower dose apixaban arm, 0.1% in the highest dose of apixaban arm and 0.5% in the placebo arm.

Doesn’t require monitoring with INR.

Should be discontinued at least 48 hours before elective surgery or invasive procedure with a moderate or high risk of bleeding.

Should be discontinued at least 24 hours before elective surgery or invasive procedures in which risk of bleeding is low or bleeding can be easily controlled.

Discontinuation of the drug is associated with increased risk of thrombotic events and if discontinued other anticoagulants should be considered, if there is no pathological bleeding.

Contraindicated in patients with active bleeding.

Should be used cautiously with other drugs that affect hemostasis, such as anticoagulants, fibrinolytic agents, aspirin, or other antiplatelet drugs, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors such as fluoxetine and serotonin-norepinephrine reuptake inhibitors such as venlafaxine.

Not recommended for patients with prosthetic heart valves.

Not recommended for patients with severe hepatic impairment.

The drug is a substrate of P-glycoprotein, as well as CYP3A4 and the concurrent use of a strong dual inhibitor of CYP3A4 and P-gp such as ketoconazole or clarithromycin increases the concentration of the drug in the dosage should be reduced or avoided.

Avoidance of concurrent use of dual inducers of CYP3A4 and P-gp such as carbamazepine, rifampin, and St. John’s wort which reduces exposure to the drug.

For stroke prevention in nonvalvular atrial fibrillation the dose is 5 mg b.i.d.

In nonvalvular atrial fibrillation dose for patients age 80 or older and with weight of 60 kg or less and a creatinine greater than 1.5 mg/dL it is 2.5 mg b.i.d.

Postoperative thromboprophylaxis for hip surgery 2.5 mg orally b.i.d. for 35 days, and for knee surgery 2.5 mg b.i.d. for 12 days.

For treatment of DVT/PE 10 mg orally twice daily for seven days followed by 5 mg orally b.i.d.

For risk reduction in recurrent DVT/PE 2.5 mg orally b.i.d.

Apixaban therapy resulted in significant lower rate of venousthromboembolism than did placebo among intermediate to high-risk ambulatory patients with cancer who were starting chemotherapy (AVERT study).