Products Affected - Description

Reason for the Shortage

• Genentech states the reason for the Cathflo Activase shortage is that rubber stopper particulate matter was found in vials after reconstitution.^1,2
• Genentech sent out a Dear Pharmacist Letter on March 22, 2013 containing information about using a 5 micron filter needle after reconstitution of Cathflo Activase.²

Available Products

Estimated Resupply Dates

Genentech has Cathflo Activase on available on allocation. All product must be filtered with a 5 micron filter needle.¹

Implications for Patient Care

• Alteplase is a recombinant tissue plasminogen activator that enhances the conversion of plasminogen to plasmin in the presence of fibrin and initiates local fibrinolysis. Alteplase is commercially available as Activase® and Cathflo Activase®.^3,4
• Cathflo Activase® is labeled to restore central venous access devices.³
• Activase® is labeled for the management of acute myocardial infarction, acute ischemic stroke, and pulmonary embolism.⁴

Safety

Rubber stopper particulate matter was found in reconstituted Cathflo Activase® vials. Genentech recommends to follow all recommended steps for the reconstitution of Cathflo Activase® and to carefully inspect the reconstituted solution for particulate matter. If no visible particulate matter is observed, attach a 5 micron filter needle to the appropriate sized syringe, and withdraw 2 mL of solution from the reconstituted vial. Remove the filter needle from the syringe and instill the appropriate dose into the occluded catheter.²

Alternative Agents & Management

• Prior to the commercial availability of Cathflo Activase®, some institutions would reconstitute a 50 mg vial of alteplase, aliquot the product, and then freeze the product until needed. However, this practice increased pharmacy workload and had a higher risk potential according to USP Chapter 797 regulations on sterile compounding.^5-12
• Other available thrombolytics include reteplase (Retavase®) and tenecteplase (TNKase®) but neither of these agents is FDA-labeled for catheter clearance.^13,14
• There are limited published data reporting the use of reteplase or tenecteplase for catheter clearance in clinical trials.^15-20
• Tenecteplase is currently available from the manufacturer but reteplase is unavailable with an estimated release date in the second quarter of 2013.^1,21

Related Shortages

• Argatroban Injection— Resolved
• Heparin Sodium Injection
• Lepirudin Injection— No Longer Available
• Reteplase Injection
• Warfarin Sodium Tablets— Resolved

1. Genentech (personal communications). February 27, March 1 and 11, April 9 and 15, and May 6, 2013.
2. Dear Pharmacist Letter- Cathflo Activase. 2013 [cited 2013 March 22]; Available from: Food and Drug Administration, Department of Health and Human Services.
3. Genentech. Cathflo Activase (Alteplase recombinant) Injection [product information]. South San Francisco, CA: Genentech, Inc.; 2011.
4. Genentech. Activase (Alteplase recombinant) Injection [product information]. South San Francisco, CA: Genentech, Inc.; 2010.
5. United States Pharmacopeial Convention. 2012 USP 35-NF 30 The Official Compendia of Standards. Rockville, MD: United Book Press, Inc.; 2012.
6. United States Pharmacopeial Convention. 2012 Second Supplement to USP 35-NF 30. Rockville, MD: United Book Press, Inc.; 2012.
7. Genentech. Activase (alteplase recombinant) data on file, Activase freezing. South San Francisco, CA: Genentech, Inc.; June 4, 2004.
8. Davis SN, Vermeulen L, Banton J, et al. Activity and dosage of alteplase dilution for clearing occlusions of venous-access devices. Am J Health Syst Pharm. 2000;57(11):1039-45.
9. Calis KA, Cullinane AM, Horne MK, et al. Bioactivity of cryopreserved alteplase solutions. Am J Health Syst Pharm. 1999;56(20):2056-57.
10. Maloney KW, Hillery CA, Nelson TJ, et al. The use of aliquoted and frozen tPA in central venous line occlusions. Blood. 1999;94(Suppl 1):29a.
11. Wiernikowski JT, Crowther M, Clase CM, et al. Stability and sterility of recombinant tissue plasminogen activator at -30 degrees C. Lancet. 2000;355:2221-2.
12. Jaffe GJ, Green GD, Abrams GW. Stability of recombinant tissue plasminogen activator. Am J Ophthalmol. 1989;108(1):90-1.
13. EKR Therapeutics. Retavase (reteplase recombinant) injection [product information]. Bedminster, NJ: EKR Therapeutics; 2009
14. Genentech. TNKase (tenecteplase) injection [product information]. South San Francisco, CA: Genentech, Inc.; 2011.
15. Baskin JL, Reiss U, Wilimas JA, et al. Thrombolytic therapy for central venous catheter occlusion. Haematologica 2012; 97(5):641-50.
16. Liu CY, Jain V, Shields AF, Heilbrun LK. Efficacy and safety of reteplase for central venous catheter occlusion in patients with cancer. J Vasc Interv Radiol. 2004;15(1 Pt 1):39-44.
17. Terrill KR, Lemons RS, Goldsby RE. Safety, dose, and timing of reteplase in treating occluded central venous catheters in children with cancer. J Pediatr Hematol Oncol. 2003;25(11):864-7.
18. Owens L. Reteplase for clearance of occluded venous catheters. Am J Health Syst Pharm. 2002;59(17):1638-40.
19. Tebbi C, Costanzi J, Shulman R et al. A phase III, open-label, single-arm study of tenecteplase for restoration of function in dysfunctional central venous catheters. J Vasc Interv Radiol. 2011; 22(8):1117-23.
20. Gabrail N, Sandler E, Charu V et al. TROPICS 1: a phase III, randomized, double-blind, placebo-controlled study of tenecteplase for restoration of function in dysfunctional central venous catheters. J Vasc Interv Radiol. 2010; 21 (12): 1852-8.
21. Cornerstone Therapeutics, formerly EKR Therapeutics, (personal communication). January 16, 2013.

Updated

Updated May 6, 2013 by Jane Chandramouli, PharmD, Drug Information Specialist. Created February 27, 2013, by Jane Chandramouli, PharmD, Drug Information Specialist. Copyright 2013, Drug Information Service, University of Utah, Salt Lake City, UT.