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Alteplase Recombinant

Last Updated: November 11, 2013
Status: Resolved

Products Affected - Description

Alteplase Recombinant Lyophilized Powder

Reason for the Shortage

  • Genentech states the reason for the Cathflo Activase shortage was 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
  • Genentech sent out a Dear Pharmacist Letter on September 23, 2013 indicating that new product with different rubber stoppers are now available and filtering is no longer needed. The new product has a purple carton and purple label on the vial to distinguish it from the old white carton and white label on the vial. The package with the white carton and white label requires filtering.3

Available Products

Cathflo Activase, Lyophilized Powder, Genentech
2 mg vial, package of 1 (NDC 50242-0041-64)


Activase, Lyophilized Powder, Genentech
50 mg vial, package of 1 (NDC 50242-0044-13)
100 mg vial, package of 1 (NDC 50242-0085-27)

Estimated Resupply Dates

Genentech has Cathflo Activase available through wholesalers. Older 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®.4,5 
  • Cathflo Activase® is labeled to restore central venous access devices.4
  • Activase® is labeled for the management of acute myocardial infarction, acute ischemic stroke, and pulmonary embolism.5

Safety

  • Use caution when reconstituting Cathflo Activase as two presentations may be on pharmacy shelves. The presentation with white labeling requires a filter needle while the other presentation with purple labeling does not.3
  • Rubber stopper particulate matter was found in reconstituted Cathflo Activase® vials in March 2013. These vials can be identified by the white packaging and labeling and require the use of a filter needle. If your pharmacy has existing supplies of the white-labeled Cathflo Activase, ensure that the product is prepared using a filter needle.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.6-13
  • Other available thrombolytics include reteplase (Retavase®) and tenecteplase (TNKase®) but neither of these agents is FDA-labeled for catheter clearance.14,15
  • There are limited published data reporting the use of reteplase or tenecteplase for catheter clearance in clinical trials.16-21
  • Tenecteplase is currently available from the manufacturer but reteplase is unavailable with an estimated release date in the second quarter of 2013.1,22

Related Shortages

References

  1. Genentech (personal communications). February 27, March 1 and 11, April 9 and 15, May 6 and 30, August 5, October 2 and 14, and November 11, 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. Dear Pharmacist Letter-Cathflo Activase with new rubber stoppers is now available and does not require filter needles. 2013 [cited 23 September 2013]; Available from Genentech.
  4. Genentech. Cathflo Activase (Alteplase recombinant) Injection [product information]. South San Francisco, CA: Genentech, Inc.; 2011.
  5. Genentech. Activase (Alteplase recombinant) Injection [product information]. South San Francisco, CA: Genentech, Inc.; 2010.
  6. United States Pharmacopeial Convention. 2012 USP 35-NF 30 The Official Compendia of Standards. Rockville, MD: United Book Press, Inc.; 2012.
  7. United States Pharmacopeial Convention. 2012 Second Supplement to USP 35-NF 30. Rockville, MD: United Book Press, Inc.; 2012.
  8. Genentech. Activase (alteplase recombinant) data on file, Activase freezing. South San Francisco, CA: Genentech, Inc.; June 4, 2004.
  9. 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.
  10. Calis KA, Cullinane AM, Horne MK, et al. Bioactivity of cryopreserved alteplase solutions. Am J Health Syst Pharm. 1999;56(20):2056-57.
  11. 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.
  12. 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.
  13. Jaffe GJ, Green GD, Abrams GW. Stability of recombinant tissue plasminogen activator. Am J Ophthalmol. 1989;108(1):90-1.
  14. EKR Therapeutics. Retavase (reteplase recombinant) injection [product information]. Bedminster, NJ: EKR Therapeutics; 2009
  15. Genentech. TNKase (tenecteplase) injection [product information]. South San Francisco, CA: Genentech, Inc.; 2011.
  16. Baskin JL, Reiss U, Wilimas JA, et al. Thrombolytic therapy for central venous catheter occlusion. Haematologica 2012; 97(5):641-50.
  17. 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.
  18. 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.
  19. Owens L. Reteplase for clearance of occluded venous catheters. Am J Health Syst Pharm. 2002;59(17):1638-40.
  20. 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.
  21. 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.
  22. Cornerstone Therapeutics, formerly EKR Therapeutics, (personal communication). January 16, 2013.

Updated

Updated November 11, 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.

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