, powder, lyophilized, for solution
Genentech, Inc.
Cathflo® Activase®(Alteplase)
Powder for reconstitution for use in central venous access devices
DESCRIPTION
Cathflo® Activase® (Alteplase) is a tissue plasminogen activator (t‑PA) produced by recombinant DNA technology. It is a sterile, purified glycoprotein of 527 amino acids. It is synthesized using the complementary DNA (cDNA) for natural human tissue‑type plasminogen activator (t‑PA) obtained from an established human cell line. The manufacturing process involves secretion of the enzyme Alteplase into the culture medium by an established mammalian cell line (Chinese hamster ovary cells) into which the cDNA for Alteplase has been genetically inserted. Fermentation is carried out in a nutrient medium containing the antibiotic gentamicin sulfate, 100 mg/L. The presence of the antibiotic is not detectable in the final product.
Cathflo Activase is a sterile, white to pale yellow, lyophilized powder for intracatheter instillation for restoration of function to central venous access devices following reconstitution with Sterile Water for Injection, USP.
Each vial of Cathflo Activase contains 2.2 mg of Alteplase (which includes a 10% overfill), 77 mg of L‑arginine, 0.2 mg of polysorbate 80, and phosphoric acid for pH adjustment. Each reconstituted vial will deliver 2 mg of Cathflo Activase, at a pH of approximately 7.3.
CLINICAL PHARMACOLOGY
Alteplase is an enzyme (serine protease) that has the property of fibrin-enhanced conversion of plasminogen to plasmin. It produces limited conversion of plasminogen in the absence of fibrin. Alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin, thereby initiating local fibrinolysis (1).
In patients with acute myocardial infarction administered 100 mg of Activase as an accelerated intravenous infusion over 90 minutes, plasma clearance occurred with an initial half‑life of less than 5 minutes and a terminal half‑life of 72 minutes. Clearance is mediated primarily by the liver (2).
When Cathflo Activase is administered for restoration of function to central venous access devices according to the instructions in DOSAGE AND ADMINISTRATION, circulating plasma levels of Alteplase are not expected to reach pharmacologic concentrations. If a 2 mg dose of Alteplase were administered by bolus injection directly into the systemic circulation (rather than instilled into the catheter), the concentration of circulating Alteplase would be expected to return to endogenous circulating levels of 5–10 ng/mL within 30 minutes (1).
CLINICAL STUDIES
Three clinical studies were performed in patients with improperly functioning central venous access devices (CVADs).
A placebo‑controlled, double‑blind, randomized trial (Trial 1) and a larger open‑label trial (Trial 2) investigated the use of Alteplase in predominately adult patients who had an indwelling CVAD for administration of chemotherapy, total parenteral nutrition, or long‑term administration of antibiotics or other medications. Both studies enrolled patients whose catheters were not functioning (defined as the inability to withdraw at least 3 mL of blood from the device) but had the ability to instill the necessary volume of study drug. Patients with hemodialysis catheters or a known mechanical occlusion were excluded from both studies. Also excluded were p |
