ADMINISTRATION ROUTES:
INTRAVENOUS
ALTERNATIVE NAMES:
Metalyse, TNK-tPA, TNKase
ICU INDICATIONS:
- Thrombolysis in acute ischaemic stroke (off-label use after consultation with Stroke service)
- Thrombolysis in massive pulmonary embolism with haemodynamic compromise (off-label use by SMO direction)
- Other selected thrombolysis indications following discussion with relevant specialty teams
Note: This monograph is a quick reference for tenecteplase dosing and administration. For full guidance on thrombolysis eligibility criteria, contraindications, monitoring requirements, and post-thrombolysis complication management, see the following policies:CC Acute Stroke Fast Track Guideline (Doc ID 1.8693) or Investigation and management of Venous Thromboembolism (Doc ID 1.100519)
PRESENTATION AND ADMINISTRATION
INTRAVENOUS:
Tenecteplase (Metalyse) 50 mg package contains:
- 1 vial containing 10,000 units (50 mg) tenecteplase
- 1 prefilled syringe containing 10 mL water for injection
Store at room temperature
Reconstitution:
- Remove tip cap from prefilled syringe and flip-off cap from the vial
- Tightly screw prefilled vial onto vial adaptor
- Keeping the vial upright, push the spike of the vial adapter into the middle of the vial stopper
- Keeping the vial upright, add the water for injection by pushing the syringe down slowly to avoid foaming
- Reconstitute by swirling gently. DO NOT shake
- Invert the vial and syringe, and transfer the required volume according to prescription into the syringe
- Disconnect the syringe from the vial-adaptor
- The final syringe contains tenecteplase at a concentration of 5 mg/mL
Intravenous Injection:
Note: Ensure all pre- and post-dose monitoring is performed in accordance with the relevant DistrictDocs policy
Central or peripharal line may be used
Administer the reconstituted solution as a single intravenous injection over 5 to 10 seconds
DO NOT administer through lines containing dextrose solutions
After administration, flush the line with 10 mL of sodium chloride 0.9%
The reconstituted solution can be stored refrigerated for up to 24 hours, or at room temperature for up to 8 hours
DOSAGE:
For both pulmonary embolism & acute ischaemic stroke, a single intravenous dose of tenecteplase (given as a bolus) is used. The dose is different for each condition.
INTRAVENOUS:
Pulmonary Embolism:
Weight-based intravenous injection dosed as below
Maximum dose 50 mg
| Weight (kg) | Dose (mg) | Volume reconstituted solution ( mL) |
|---|---|---|
| < 60 | 30 | 6 |
| 60 - 69 | 35 | 7 |
| 70 - 79 | 40 | 8 |
| 80 - 89 | 45 | 9 |
| ≥ 90 | 50 | 10 |
Acute ischaemic stroke:
0.25 mg/kg intravenous injection
Maximum dose 25 mg
Note: Round the calculated dose volume to the nearest 0.1 mL before administration. For example, a 69 kg patient requires 17.25 mg of tenecteplase, equivalent to 3.45 mL of the reconstituted 5 mg/mL solution. Administer 3.5 mL.
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPIES:
Dose in renal impairment:
Dose as in normal renal function
Dose in renal replacement therapy:
Dose as in normal renal function
DOSAGE IN LIVER FAILURE:
Severe liver impairment:
Tenecteplase can accumulate in severe liver impairment. Carefully review the risk of bleeding versus the benefits of thrombolysis, especially in patients with coagulopathy.
DOSAGE IN PAEDIATRICS:
Tenecteplase is not routinely used in paediatric patients
Alteplase is the preferred thrombolytic agent:
- See Starship Guideline for the Treatment of Paediatric Stroke.
- For other indications, dose as advised by Starship or Wellington Paediatricians
CLINICAL PHARMACOLOGY:
- Onset of action: immediate
- Duration of action: ~ 90 min
- Elimination: fully cleared from the plasma in approximately 9 – 11 hours
Tenecteplase is a genetically modified form of human tissue plasminogen activator (tPA)
Mechanism:
- Binds preferentially to fibrin within thrombi
- Converts plasminogen to plasmin
- Plasmin degrades fibrin, producing clot dissolution
Compared with alteplase, tenecteplase has:
- Increased fibrin specificity
- Greater resistance to plasminogen activator inhibitor-1
- Longer plasma half-life allowing single bolus administration
CONTRAINDICATIONS:
Absolute contraindications differ depending on the indication for thrombolysis. Refer to the relevant hospital policy described above.
WARNINGS:
Bleeding:
The major adverse effect is bleeding, including intracranial or uncontrolled haemorrhage.
Bleeding risk is increased with:
- Anticoagulants
- Antiplatelet agents
- Recent invasive procedures
- Trauma
- Uncontrolled hypertension
After thrombolysis, avoid:
- Intramuscular injections
- Unnecessary invasive procedures
- Arterial punctures unless essential
Carefully monitor:
- Puncture sites
- Drains
- Urine
- Neurological status
Recent procedures:
Careful assessment is required following:
- Central venous access
- Arterial catheter insertion
- Surgery
- CPR-related trauma
Hypersensitivity reactions:
Hypersensitivity reactions (anaphylaxis, urticaria, angioedema, laryngeal oedema, rash) have been reported after administration. Monitor closely for hypersensitivity reactions while administering the dose, and for several hours after.
PRECAUTIONS:
General:
See WARNINGS. Careful assessment of bleeding risk is required before administration.
Laboratory Tests:
No laboratory tests are required in addition to routine ICU monitoring. As tenecteplase is a fibrinolytic, fibrinogen levels will decrease (although less so than with alteplase) and D-dimer & FDP will increase. PT/INR may be normal or slightly prolonged.
Drug/Laboratory Test Interactions:
None known
IMPORTANT DRUG INTERACTIONS IN ICU:
Increased bleeding risk with:
- Anticoagulants: unfractionated heparin, low molecular weight heparin, warfarin, direct oral anticoagulants
- Antiplatelet agents: aspirin, P2Y12 inhibitors (clopidogrel, ticagrelor), glycoprotein IIb/IIIa inhibitors (eptifibatide, tirofiban)
- Defibrotide
ADVERSE REACTIONS:
Cardiovascular:
Reperfusion arrhythmias (when used for thrombolysis of STEMI), hypotension (rare), heart failure, cardiogenic shock
Neurological:
Intracranial haemorrhage, neurological deterioration due to bleeding
Haematological:
Major bleeding, haemorrhage at puncture sites, gastrointestinal bleeding, haematuria
Immunological:
Hypersensitivity reactions (rare)
ADDITIONAL REFERENCES:
- Capital Coast Acute Stroke Fast Track Guideline (Doc ID 1.8693)
- Investigation and management of Venous Thromboembolism (VTE) (Doc ID 1.100519)