Drotrecogin Alfa Brand Name– Xigris
What is Drotrecogin Alfa
Although originally approved for treatment of severe sepsis, Xigris (drotrecogin alfa) was voluntarily withdrawn from worldwide markets in October 2011 based on data from the PROWESS-SHOCK trial.
A preliminary analysis of the trial failed to demonstrate survival benefit, with 28-day all cause mortality rates for drotrecogin alfa-treated (n = 846) and placebo-treated (n = 834) patients being 26.4% and 24.2%, respectively (RR = 1.09; 95% CI 0.92—1.28, P = 0.31).
Health care providers are advised to discontinue drotrecogin alfa in any patients currently receiving treatment.
Additionally, all remaining drotrecogin alfa product should be returned to the supplier from which it was purchased.
Drotrecogin alfa (activated) is a recombinant human activated protein C (rhAPC) product.
Drotrecogin alfa is produced in a mammalian cell line into which the complementary DNA for the human protein C has been inserted.
The cells secrete the inactive protein into the fermentation medium and the human protein C is enzymatically activated by cleavage with thrombin and subsequently purified.
Drotrecogin alfa has the same amino acid sequence and the same sites of glycosylation, although some differences in glycosylation structures exist, as human plasma-derived activated protein C.
Drotrecogin alfa is approximately 55kDa, consisting of a heavy chain and a light chain linked by a disulfide bond.
Activated protein C is a natural anticoagulant serine protease with potent antithrombotic and antiinflammatory properties.
Approval of drotrecogin alfa for treatment of severe sepsis was based on results from the PROWESS trial.
This phase III trial was terminated early after an interim review determined a significant reduction in 28-day mortality for the treatment group as compared to the placebo group (24.7% vs. 30.8%). Treatment with drotrecogin alfa was associated with a 19.4% reduction in the relative risk of death and a 6.1% absolute reduction in the risk of death.
Mortality reduction does not appear to occur with use of the drug in patients under 18 years of age or in adults with single organ dysfunction and recent surgery.
The use of protein C in the management of sepsis due to severe meningococcemia has been found to improve purpura fulminans and decrease the number of amputations in a small number of patients.
The Biologics License Application for drotrecogin alfa was submitted to the FDA and granted priority review in January 2001.
The FDA approved drotrecogin in November 2001.
Indications
- sepsis
Side Effects
- antibody formation
- bleeding
- bleeding
- ecchymosis
- GI bleeding
- intracranial bleeding
- retroperitoneal bleeding
- thromboembolism
- thrombosis
Monitoring Parameters
- D-dimer
Contraindications
- alcoholism
- aneurysm
- anticoagulant therapy
- arteriovenous malformation
- bleeding
- brain tumor
- breast-feeding
- children
- coagulopathy
- dialysis
- epidural anesthesia
- GI bleeding
- head trauma
- hemophilia
- hepatic disease
- human immunodeficiency virus (HIV) infection
- hypotension
- intracranial mass
- jaundice
- metabolic acidosis
- oliguria
- organ transplant
- pancreatitis
- peptic ulcer disease
- pregnancy
- respiratory insufficiency
- retroperitoneal bleeding
- shock
- stroke
- surgery
- thrombocytopenia
- thrombolytic therapy
Interactions
- Abciximab
- Amlodipine; Celecoxib
- Anagrelide
- Anticoagulants
- Antithrombin III
- Apixaban
- Argatroban
- Aspirin, ASA; Dipyridamole
- Betrixaban
- Bivalirudin
- Celecoxib
- Cilostazol
- Clopidogrel
- Dabigatran
- Dalteparin
- Danaparoid
- Desirudin
- Diclofenac
- Diclofenac; Misoprostol
- Diflunisal
- Diphenhydramine; Ibuprofen
- Diphenhydramine; Naproxen
- Dipyridamole
- Edoxaban
- Enoxaparin
- Eptifibatide
- Esomeprazole; Naproxen
- Etodolac
- Famotidine; Ibuprofen
- Fenoprofen
- Flurbiprofen
- Fondaparinux
- Heparin
- Hydrocodone; Ibuprofen
- Ibuprofen
- Ibuprofen; Oxycodone
- Ibuprofen; Pseudoephedrine
- Indomethacin
- Ketoprofen
- Ketorolac
- Lansoprazole; Naproxen
- Lepirudin
- Meclofenamate Sodium
- Mefenamic Acid
- Meloxicam
- Nabumetone
- Naproxen
- Naproxen; Pseudoephedrine
- Naproxen; Sumatriptan
- Nonsteroidal antiinflammatory drugs
- Oxaprozin
- Pentosan
- Piroxicam
- Platelet Inhibitors
- Prasugrel
- Rivaroxaban
- Rofecoxib
- Salicylates
- Sulindac
- Thrombolytic Agents
- Ticagrelor
- Ticlopidine
- Tinzaparin
- Tirofiban
- Tolmetin
- Valdecoxib
- Vorapaxar
- Warfarin
