Introduction

The transition from alteplase (ALT) to tenecteplase (TNK) in the management of acute ischemic stroke (AIS) has been an exciting and thoroughly discussed topic within the neurocritical care community. Although debates on the clinical efficacy and safety of TNK for AIS have subsided somewhat in light of recently published data, what remains lacking is a clear “road map” for institutions on how to properly implement the transition in thrombolytics. This article will attempt to serve as a guide for those evaluating the transition from ALT to TNK for AIS and shares the experience from our institution’s rollout.

Safety

With respect to the most feared adverse event with TNK use, symptomatic hemorrhagic conversion, data suggest that incidence rates are relatively similar to ALT. However, other safety concerns exist that have been omitted in the literature.

Lastly, TNK has multiple indications for use—some FDA approved and some not—and it is imperative to have a discussion on the extent of TNK use for non-AIS indications. There are minimal data for TNK use in the pulmonary embolism literature but extensive data on its use in myocardial infarction. Additionally, stroke programs must consider which thrombolytic will be used and how it should be supplied for cases of AIS that require intra-arterial administration.

Figure 1. Example of a stroke kit.
Another large concern for stroke programs is ensuring that appropriate dosing is utilized for AIS. This may seem like a relatively simple concept, but TNK is currently supplied in a box that emphasizes dosing for myocardial infarction. This could lead to the possibility that in a critical moment, the wrong dosing could be utilized for AIS. To mitigate this, many programs have removed TNK from the manufacturer-supplied box entirely and utilized custom “stroke kits” (Figures 1 & 2)

For all the reasons presented above, each institution should discuss current indications where thrombolytics have a place in therapy and decide which agent will be utilized for that situation. In evaluating these situations, institutions should also determine where thrombolytics will be stocked/located (i.e., central pharmacy, satellite pharmacy, or automated dispensing cabinet [ADC]), and whether medication errors can be mitigated by removing one or the other, while also considering the time sensitive nature associated with thrombolytic use. If multiple thrombolytics will be stocked in the ADC, safeguards should be present in terms of override capability and user access. The final safeguards that can be utilized to prevent errors are personnel double checks and warnings within the electronic health record (EHR).

Education

Proper education of staff involved in handling TNK and responding to stroke alerts is a vital step in the transition from ALT to TNK. Education will help to ensure that institutional guidelines are being followed and staff are maintaining patient safety. This education should be widespread and include pharmacy staff, providers, and nursing colleagues. Pharmacy staff will need education on the process of how TNK will be supplied, whether in dedicated TNK “stroke kits” or in the current manufacturer-supplied box. If a “stroke kit” is being used, there should be specific education on the contents of the kit to ensure accuracy. Further, the location of TNK should be identified for pharmacists and nursing staff to ensure timeliness of administration.

Providers should also be educated on how to order TNK and how the order may differ from ALT. Implementation of TNK order sets for AIS can help streamline the order entry process and mitigate dosing errors. It will also be important to note the differences in order sets depending on the indication. For institutions that will have both TNK and ALT on their formulary, education on when to use each agent and the correct order set for that agent and indication will be necessary.

Nursing staff should be educated on the proper dilution, dosing, and administration of TNK. It is important to differentiate the dosing for AIS and other indications and ensure nursing staff is aware of the maximum dose for AIS. Nursing should also be educated that TNK is given as a one-time bolus instead of a bolus with an infusion like ALT. However, it should be emphasized that patients who receive TNK should be monitored just as closely as those who had received ALT in the past, even though the administration time is shorter. Continuous education should also be given based on an institution’s progress with the transition and to address any issues that may arise. Lastly, all personnel should be educated on how to report adverse events and voice concerns to ensure problems are addressed in a timely manner.

Operational Concerns & Preparation

There are many moving parts when discussing the operational aspects of changing from ALT to TNK for AIS. The first step after the decision to switch is made is to discuss implementation policies and guideline changes with your institution’s pharmacy and therapeutics committee. You should also coordinate with your telestroke services, neurology providers, and other collaborators to inform them of the switch to maintain clear, streamlined communication. Orders sets will also need to be updated and tested in the EHR. As discussed above, education should be completed in a systematic way to ensure all team members involved in the AIS pathway are educated prior to the go-live date.

If an institution decides that moving toward a custom “stroke kit” for AIS is appropriate, the contents of the kit should be thoroughly discussed. In order to prepare the “stroke kit” for use in AIS, the TNK should be removed from the manufacturer’s box and package insert, as the kit should include all necessary items for mixing and dosing. TNK dosing cards with weight, dose, and volume should be included to assist with dosing and avoid medication errors in case a pharmacist is not available at the bedside.

In order to create an effective kit, we recommend the following in a sealable plastic bag:

• TNK vial
• 2 alcohol pads
• 5 mL dose syringe
• dosing card
• blank label
• needleless cannula
• separate sealable plastic bag for the diluent materials (which includes the diluent, 10 mL diluent syringe, and needleless cannula)

Pharmacists will need to play a key role at the bedside to ensure safe, accurate, and timely administration of the medication. Communications departments should therefore be made aware to ensure stroke pages include clinical pharmacists. Pharmacists can also assist in assessing the blood pressure and recommending pharmacologic agents to reduce the blood pressure levels to goal prior to administration of TNK. Additionally, they can make sure a blood glucose level has been drawn, as TNK is incompatible with dextrose-containing fluids. It is also recommended to have a second check dose calculation to ensure the appropriate dose is administered.

Cost & Billing

One of the big discussion points on the change from ALT to TNK revolves around the cost of the medications. Average wholesale prices of TNK are lower than ALT both within the United States and in most other countries. From a drug billing standpoint, AIS is typically placed in a diagnosis-related group (DRG) that confers a standardized hospital reimbursement. In turn, all the care provided for a patient with AIS is billed as a package option and covered under this reimbursement. DRG-based billing is commonly used by Medicare, Medicaid, and some commercial insurances which is important given that the amount of drug used versus wasted should be accounted for in these billing practices.

These factors are important when creating orderable items for TNK and on the backend for billing purposes. The change from a clinical standpoint is a rather easy process, but the process of changing billing mechanisms is more complicated and one that should be thoroughly discussed prior to the go-live of the new AIS protocol.

Conclusion

Transitioning from ALT to TNK for AIS remains a widely discussed topic for many stroke programs. There are many factors involved with the transition, including implementation of safeguards to prevent dosing and administration errors, education across all disciplines comprising the stroke response team, and operational considerations that vary between ALT and TNK. A structured checklist-based approach should be considered for programs preparing to make the switch, and hopefully this article can serve as a template.

Table 1: Tenecteplase for Institutional Transition Checklist