Lixiana - Edoxaban

What is Lixiana and Edoxaban used for?

Lixiana is an anticoagulant medicine (a medicine that prevents the formation of blood clots) used in adults:

for the prevention of stroke (caused by blood clots in the brain) and systemic embolism (blood clots in other organs) in patients suffering from non-valvular atrial fibrillation (rapid and irregular contractions of the upper chambers of the heart). It is used in patients who have one or more risk factors, such as a previous stroke, high blood pressure, diabetes, heart failure or age 75 or older;
for the treatment of deep vein thrombosis (DVT, blood clot in a deep vein, usually in the leg) and pulmonary embolism (clot in a pulmonary blood vessel) and the prevention of recurrence of DVT and pulmonary embolism.

Lixiana contains the active ingredient edoxaban.

How is Lixiana - Edoxaban used?

Lixiana is available as tablets (15, 30 and 60 mg) and can only be obtained with a prescription. The usual dose is 60 mg once a day. Therapy is continued until the benefit exceeds the risk of bleeding, which depends on the disease being treated and on any existing risk factors. Doses should be halved in patients with moderately or severely reduced kidney function, in low body weight patients or in patients taking concomitantly some medicines (known as P-gp inhibitors) that may interfere with the elimination of edoxaban from the body. A dose adjustment may also be necessary in patients switching from Lixiana to other anticoagulant medicines or vice versa. For more information, see the package leaflet.

How does Lixiana - Edoxaban work?

The active substance in Lixiana, edoxaban, is a "factor Xa inhibitor". This means that it blocks factor Xa, an enzyme that intervenes in the production of thrombin. Thrombin is essential for blood clotting. By blocking factor Xa, the medicine reduces blood thrombin levels, thus helping to treat clots and reduce the risk of clot formation in the arteries and veins resulting in the development of DVT, pulmonary embolism, stroke or other organ damage .

What benefit has Lixiana - Edoxaban shown during the studies?

Lixiana has shown to be as effective as the standard warfarin anticoagulant in preventing stroke and systemic embolism in patients with atrial fibrillation. The effects were investigated in a main study involving over 21, 000 patients for an average of 2.5 years. The main measure of effectiveness was the rate of stroke or systemic embolism detected among patients each year. A first event of systemic embolism or stroke occurred in 182 patients treated with standard doses of Lixiana and in 232 patients treated with warfarin, corresponding to annual rates of these events of approximately 1.2% and 1.5 respectively %. When another recommended definition of the type of stroke was used, embolism or stroke due to blood clots were observed in 143 patients treated with Lixiana (0.9%) and 157 patients treated with warfarin (1%). The results tended to be better in patients with reduced kidney function than in those with normal renal function.

Also in the treatment and prevention of blood clots in patients with DVT or pulmonary embolism, Lixiana demonstrated efficacy equal to that of warfarin in a study of over 8 200 patients. The main measure of effectiveness was the number of patients who had another episode of DVT or pulmonary embolism during the study period. Additional episodes were observed in 130 of the 4 118 patients treated with edoxaban (3.2%) and in 146 of the 4 122 patients treated with warfarin (3.5%).

What is the risk associated with Lixiana - Edoxaban?

The most common side effects with Lixiana (which may affect up to 1 in 10 people) are skin and soft tissue bleeding, nasal bleeding (epistaxis) and vaginal bleeding. Bleeding can occur at any site and can be severe or even fatal. Other common side effects are anemia (low levels of red blood cells), rash and abnormal liver function tests. For the full list of all side effects reported with Lixiana, see the package leaflet.

Lixiana should not be used in patients with ongoing bleeding, liver disease that affects blood clotting, uncontrolled high blood pressure, or a disease that carries a significant risk of severe bleeding. It must also not be used in women who are pregnant or breastfeeding or in patients treated concomitantly with another anticoagulant. For the full list of limitations, see the package leaflet.

Why has Lixiana - Edoxaban been approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Lixiana's benefits are greater than its risks and recommended that it be approved for use in the EU. The medicine has been shown to be at least as effective as warfarin in reducing stroke rates in patients with atrial fibrillation and in preventing further episodes of DVT or pulmonary embolism. However, the benefits in stroke prevention in atrial fibrillation tend to be less evident in patients with high creatinine clearance (good renal function) and this requires further study.

Regarding safety, overall the risk of severe bleeding, such as intracerebral hemorrhage, is reduced compared to warfarin, although the difference may be less if warfarin treatment is effectively managed. Although there has been a greater risk of mucosal bleeding (the tissues lining the body's cavities, such as the nose, intestine, vagina), the committee believes that the risk can be managed with appropriate measures.

What measures are being taken to ensure the safe and effective use of Lixiana - Edoxaban?

A risk management plan has been developed to ensure that Lixiana is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Lixiana, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Lixiana will provide information material for the doctors who prescribe the medicine and an alert card for patients, which explains the bleeding risks associated with the medicine and how to manage them. It will also conduct a study on the effects of the medicine in patients with atrial fibrillation and good kidney function.