Review of Factor Xa Inhibitors Uses, Side Effects, Reversal, Efficacy, and Mechanism | Cecilia Pham, PharmD | RxEconsult

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Eliquis, Xarelto, Arixtra Uses, Side Effects, Efficacy Category: Anticoagulation (clot prevention) by - December 12, 2012 | Views: 25205 | Likes: 0 | Comment: 0  

Factor Xa Inhiitors

What Factor Xa inhibitor drugs are approved in the US

There are 3 factor Xa inhibitors approved by the FDA in the US. They are fondaparinux (Arixtra), rivaroxaban (Xarelto), and apixaban (Eliquis). Arixtra is an injectable drug while Xarelto and Eliquis are oral medications.

What are Factor Xa inhibitors used for

Factor Xa inhibitors are used for treating and preventing blood clots in the deep veins [deep vein thrombosis (DVT)] in patients undergoing surgeries for hip fracture, hip or knee replacement, or the abdomen. This class of drugs can also be used for treatment of blockage in the arteries of the lungs caused by a blood clot originating from another location (pulmonary embolism). Xarelto and Eliquis are also used for prevention of stroke and blood clots in patients with nonvalvular atrial fibrillation (a type of abnormal heart rate and rhythm)

How do Factor Xa inhibitors work (mechanism)

Xarelto and Eliquis directly bind to the clotting enzyme called Factor Xa. By doing so, the Factor Xa cannot associate with other clotting factors to start the biological cascade that results in the formation of a blood clot. Arixtra indirectly blocks the action of Factor Xa by using the body’s natural clot inhibiting enzyme called antithrombin III. This enzyme binds to Factor Xa, which again blocks the biological pathway in producing blood clots.

What are the major side effects of Factor Xa inhibitors

The major side effects are mainly bleeding complications. Arixtra is an injectable that could cause mild irritation, rash, and itchiness at the injection site. Fever and anemia may also occur with the Factor Xa inhibitors.

Factor Xa inhibitors have no established antidotes for reversal. Reversal agents for Factor Xa inhibitors are being evaluated. About 1 to 4 percent of patients treated with Factor Xa inhibitors may develop major bleeding, and 1 percent may require emergency surgery that requires quick reversal of the agents. 

How safe and how well do Factor Xa inhibitors work compared to other anticoagulants

A double-blinded study randomized over 14,000 patients to Xarelto 20 mg and 15 mg to warfarin in preventing stroke and clotting events in non-valvular atrial fibrillation. 3.8% of patients on Xarelto versus 4.3% of patients on warfarin had stroke or clotting events. Xarelto (4.3%) had more bleeding events than warfarin (3.1%). Xarelto was not superior to warfarin in this study.

Xarelto 10 mg was compared to enoxaparin 40 mg for preventing DVT after hip or knee replacement surgery among 9,000 randomized patients in three double-blinded trials with different drug exposure times. The Xarelto group had much less clotting events compared to the enoxaparin group (1.1% versus 3.9%; 2% versus 8.4%, 9.7% versus 18.8%). Major bleeding events were similar between Xarelto (5.8%) and enoxaparin (5.6%).

A double-blinded study randomized over 1,600 patients for up to 9 days compared Arixtra 2.5 mg to enoxaparin 40 mg in preventing clotting events after hip fracture surgery. Enoxaparin treated patients (19.1%) had twice as many clotting events as Arixtra treated patients (8.3%). Major bleeding events were similar between Arixtra (2.2%) and enoxaparin (2.3%).

Two double-blinded studies randomizing over 2,000 patients per trial compared Arixtra 2.5 mg to enoxaparin 60 mg or 40 mg in preventing clotting events in hip replacement surgery. After an up-to-9 day treatment period, Arixtra had less clotting events (6.1% and 4.1%) than enoxaparin (8.3% on 60 mg and 9.2% on 40 mg).

Another double-blinded study randomizing over 1,000 patients compared Arixtra 2.5 mg to enoxaparin 60 mg for preventing clotting events post knee replacement surgery. After an up-to-9 day treatment, enoxaparin had more than twice as much clotting events 27.8%) than Arixtra (12.5%). However, Arixtra (2.1%) had more major bleeding events than enoxaparin (0.2%).

Approximately 3,000 patients were randomized in a double-blinded study comparing Arixtra 2.5 mg to dalteparin 5,000 units, for up to 9 days, in preventing clotting events post abdominal surgery. 4.6% of patients on Arixtra had clotting events versus 6.1% on dalteparin. 3.4% of patients had major bleeding with Arixtra versus 2.4% with dalteparin.

In the treatment of DVT, a double-blinded study randomizing over 2,000 patients compared Arixtra 5 mg, 7.5 mg, 10, mg to enoxaparin 1mg/kg every 12 hours for up to 9 days. Blood clots occurred in 3.9% of Arixtra treated patients and 4.1% of enoxaparin treated patients.

Eliquis 5 mg twice daily was more effective than warfarin in preventing stroke and blood clots in patients with nonvalvular atrial fibrillation. Eliquis was specifically more effective in preventing strokes caused by bleeding in the brain. Eliquis was associated with fewer major bleeds than warfarin.

Helpful Resources and References

Arixtra Prescribing Information

Xarelto Prescribing Information

Eliquis Prescribing Information

Patel MR, Mahaffey KW, Garg J, et al; for the ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-891.

The EINSTEIN Investigators: Bauersachs R, Berkowitz SD, Brenner B, et al. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. N Engl J Med 2010;363(26):2499-2510.

Albertsen, I. et al. September 10, 2012. Prevention of Venous Thromboembolism with New Oral Anticoagulants versus Standard Pharmacological Treatment in Acute Medically Ill Patients: A Systematic Review and Meta-Analysis. Drugs. 72(13): 1755-1764.

Goldhaber, SZ; et all. 2011. Apixaban versus enoxaparin for thrombroprophylaxis in medically ill patients. N Engl J Med. 365 (23): 2167-77.

The Magellan Study on Rivaroxaban

Donath, L. et al. December 2012. Efficacy and safety of venous thromboembolism prophylaxis with fondaparinux or low molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery - findings from the ORTHO-TEP registry. British Journal of Clinical Pharmacology. 74(6): 947-958.

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Updated 3/30/14

This medication summary is for information only and is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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