MEDICINAL PRODUCT NO LONGER AUTHORIZED
What is Xigris?
Xigris is a powder contained in a vial that has to be diluted in a drip solution (slow injection into a vein).
The active substance is drotrecogin alfa (activated).
What is Xigris used for?
Xigris is used in adults with severe sepsis, which is the presence of bacteria in the bloodstream that produce harmful substances (toxins). The toxins cause a functional insufficiency of the various organs (heart, lungs, kidneys, etc.). Xigris is used in case of multi-organ failure (of at least two organs) and in addition to the best therapies provided for the specific case. Xigris should be used mainly if the therapy can be started within 24 hours of the onset of the insufficiency. Xigris is a short-term therapy medicine.
The medicine can only be obtained with a prescription.
How is Xigris used?
Xigris should be used by medical experts who work in healthcare facilities specializing in the care of patients with severe forms of sepsis. Xigris should be administered via a drip. The recommended dose is 24 micrograms per kilogram of body weight per hour and should be administered continuously for 96 hours. The optimal method of administration is through an infusion pump, as this method ensures an adequate control of the infusion rate. Xigris should be used within 48 hours of the onset of insufficiency; the best results are obtained by starting the treatment within 24 hours of this onset. Xigris should not be used in children.
How does Xigris work?
One of the problems that occur in severe forms of sepsis is excessive blood clotting, as the clots that form can block the flow of blood to vital organs of the body, such as the kidneys and lungs. Xigris is an anticoagulant, meaning it prevents the formation of blood clots. The active ingredient in Xigris is drotrecogin alfa (activated), a substance very similar to the anticoagulant naturally present in the body, activated protein C. Drotrecogin alfa (activated) is produced with so-called 'recombinant DNA technology'; this technique involves the insertion of a gene (DNA) into a cell, which thus becomes capable of producing drotrecogin alfa. Once introduced into the body, drotrecogin alfa limits the production of thrombin, one of the factors responsible for coagulation, also reducing the inflammation caused by the infection. The use of Xigris in patients with sepsis reduces the risk of forming dangerous clots.
What studies have been carried out on Xigris?
The efficacy of Xigris in severe forms of sepsis has been evaluated in two studies. The PROWESS study compared Xigris with a placebo on 1690 patients. The ENHANCE study was conducted on over 2, 000 patients treated with Xigris. Another study (ADDRESS) was conducted on almost 3, 000 patients with severe sepsis but reduced risk of death, comparing Xigris with a placebo. All studies assessed the 28-day mortality rate reduction.
What benefit has Xigris shown during the studies?
At 28 days, the number of deaths was lower among patients treated with Xigris compared to patients treated with placebo. This emerged most clearly when Xigris was administered within 24 hours of the onset of failure and in patients with multiorgan failure. These results indicate the desirability of administering Xigris as soon as insufficiency appears, so its use is recommended within 24 hours of its inception.
What is the risk associated with Xigris?
The most common side effect, as for other anticoagulants, is bleeding. For the full list of all side effects reported with Xigris, see the Package Leaflet.
Xigris should not be used in people who may be hypersensitive (allergic) to drotrecogin alfa (activated), thrombin bovine (animal protein derived from cows) or any of the components of the medicine, and in patients with chronic liver disease or brain tumor . Xigris should not be used in patients with ongoing bleeding or at risk of bleeding; for the complete list of limitations, see the package leaflet. The concomitant administration of Xigris and other anticoagulants (such as warfarin and high dose heparin) should be carefully evaluated by the doctor; the complete list is reported in the Summary of Product Characteristics (included with the EPAR).
Why has Xigris been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that the benefits of Xigris outweigh the risks in the treatment of patients with severe sepsis and multi-organ failure. The committee therefore recommended that Xigris be given marketing authorization. Xigris was authorized "in exceptional circumstances". This means that it was not possible to obtain complete data on Xigris. Every year, the European Medicines Agency (EMEA) will review any new data that has become available and, if necessary, update this summary.
What information is still awaited for Xigris?
The company that makes Xigris has committed to conducting a further study to assess the safety and efficacy of Xigris in patients with severe sepsis.
More information on Xigris
On 22 August 2002, the European Commission issued a marketing authorization valid throughout the European Union to Eli Lilly Nederland BV for Xigris. The authorization was renewed on 22 August 2007.
For the full version of the evaluation (EPAR), click here.
Last update of this summary: August 2007
