Monday, June 13, 2016

Replacement for Unused Alteplase (tPA)

A 78-year-old female with acute onset of right-sided weakness, facial droop, and slurred speech presents via ambulance to your emergency department (ED). After CT and labs are completed, the neurology team decides to administer alteplase (tPA) for acute ischemic stroke and the pharmacist begins reconstituting the medication. However, the family arrives and states they do not want the patient to receive tPA. What should you do with the reconstituted product that is now not to be administered to the patient?

Although posted on Genetech’s website, many pharmacists may be unaware that Activase® can be returned for replacement if it is mixed and not administered under certain situations. According to the Activase Spoilage Replacement Program, when the medication is “… prescribed for a labeled indication and unable to be administered, the product might be eligible for replacement.” As tPA is FDA-approved for the treatment of acute submassive PE, STEMI, and acute ischemic stroke, tPA that is reconstituted for any of these indications is potentially eligible for replacement. A Spoilage Replacement Form is required to be completed and faxed to the manufacturer for review and approval of replacement. More detailed information regarding how to obtain and submit the Spoilage Replacement Form can be found here.

Potential reasons for replacement include:
  • Delivery system failure 
  • Patient/family refused 
  • Patient missed time window/time elapsed 
  • Patient expired/coded prior to administration 
  • Patient transferred to a medical floor 
Based on the reasons above, there is a wide range of possible situations in which a replacement may be eligible. The eligibility criteria have been updated in the past year and unfortunately are now more stringent as several reasons for replacements were removed such as “Contraindicated/Misdiagnosed,” “Physician Preference,” “Duplicate Reconstitution,” and “Admixture Error.”

Here are some tips for maximizing the chances of replacement of unused alteplase:
  • Return all product to the vial 
    • This includes the bolus and waste and as much volume as possible from the IV tubing if you have primed it 
    • Given the potential for replacement, never dispose of the waste until the product is actually infusing into the patient in case the situation changes at the last second 
  • Keep everything 
    • If possible, return the drug vial, diluent vial, and box to Genetech 
    • Returning everything increases the chances of a replacement as some representatives may require everything (including the box) be returned for eligibility
  • Write an explanation as soon as possible 
    • The Spoilage Replacement Form requires a “detailed explanation of how the spoilage occurred” 
    • The sooner you write your explanation the better as you may forget or leave out pertinent information if completed at a later date 
  • Although not listed formally in the “Potential reasons for replacement” section, there is a checkbox for “other” as a reason for spoilage 
    • If you have a compelling situation in which the medication was prepared but ultimately withheld and does not meet the criteria, try to explain in attempts to ensure that replacement can occur 
As the EM pharmacist is intimately involved with the care of these patients, you have a great opportunity to help the pharmacy department’s budget by identifying situations to request a replacement for unused product. Acquisition costs for tPA are approximately $10,000/dose and any replacement product you can obtain will be a substantial win for your department’s bottom line. Work with your pharmacy manager or buyer to develop a system for requesting replacements and assigning the various required tasks.

If the product is not eligible for a replacement based on the reasons above, consider saving the medication for use on another patient as per the package insert, tPA can be used within 8 hours of reconstitution. If you work in a busy stroke center you’ll likely see additional stroke patients within those 8 hours and can potentially utilize the previous vial instead of mixing a new one.

As a last resort for unused tPA, instead of disposing it, consider using it as an educational tool for pharmacists and pharmacy technicians at your institution. Pharmacy personnel who may not be as experienced reconstituting tPA can benefit from the hands-on practice with real vials and transfer devices.

*** UPDATE ***
As of November 15, 2016 Genentech’s new Spoilage Replacement Request Form has gone into effect with several updates compared to the previous form including a revised list of spoilage reasons. Thankfully, this list has expanded and now aligns with the package insert list of contraindications and also includes patients whose symptoms have significantly improved.

Eleven new potential reasons for replacement include:
  • Active internal bleeding
  • Bleeding diathesis (February 2016 update of package insert does not state specific laboratory cutoffs)
  • Current intracranial hemorrhage
  • Current severe uncontrolled hypertension (February 2016 update of package insert does not state specific cutoffs)
  • History of recent stroke (for PE/AMI patients only)
  • Intracranial conditions that may increase risk of bleeding
  • Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma
  • Subarachnoid hemorrhage
  • History of cerebrovascular accident
  • Intracranial neoplasm, arteriovenous malformation, or aneurysm
  • Patient symptoms returned to a nondisabling deficit
Four reasons have remained unchanged:
  • Patient/family refused product
  • Patient missed time window/time elapsed
  • Patient expired/coded prior to administration
  • Other medical reason, not listed above
Two reasons for replacement have been removed:
  • Delivery system failure
  • Patient transferred to a medical floor
Additional updates to the Spoilage Replacement process include:
  • The replacement instructions now specifically state: “Please retain all original product packaging for returns processing”
    • As mentioned previously, returning everything possible (including the box) will increase your chances of replacement
  • Inclusion of product’s serial number on the Spoilage Replacement Form (in addition to NDC and Lot numbers)
  • Requirement that a Physician or Director of Pharmacy sign the attestation section
    • This new requirement may necessitate changes in your institution's current process for tPA replacement to decide who will be responsible for signing off forms to be submitted
  • Changes to the timeframe requirements for replacement
    • The Spoilage Replacement Form must be faxed within 30 days from the date of spoilage occurrence
    • The unused product must be returned to Genentech within 60 days from the date of Genentech approval of the spoilage request (or a valid Certificate of Destruction)

Overall, the new expanded list of reasons for replacement is a big win. This new list will now encompass a larger percentage of stroke patients and hopefully increase the number of successful product returns and decrease the costly waste associated with unused tPA.

Scott Dietrich, PharmD (@PCC_PharmD)
EM Clinical Pharmacist
University of Colorado Health - North
Fort Collins, Colorado

Peer reviewed by Craig Cocchio, PharmD, BCPS (@iEMPharmD) and Nadia Awad, PharmD, BCPS (@Nadia_EMPharmD)

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