Product Information
Product Information
What is tenecteplase?
Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA. It is supplied by Boehringer Ingelheim as Metalyse®.
Metalyse® 5000 units (25mg) is indicated in adults for the intravenous thrombolytic treatment of acute ischaemic stroke (AIS) within 4.5 hours from the last known well and after exclusion of intracranial haemorrhage.1
Chemistry of Metalyse®
Tenecteplase is recombinant DNA derived a glycoprotein consisting of 527 amino acids. It is produced by modifying the complementary DNA (cDNA) for natural human tissue plasminogen activator (t-PA) at three key sites2:
- Adding a new glycosylation site on kringle-1 by substituting threonine-103 with asparagine (T103N)
- Removing the existing glycosylation on kringle-1 by substituting asparagine-117 with glutamine (N117Q)
- Substituting with a tetra-alanine at positions 296-299 [KHRR(296-299)AAAA] in the protease domain
The drug name tenecteplase or TNK-tPA is named after the three amino acids: T, N, and K, that were altered at three positions.2
Due to these modifications, Metalyse® has a prolonged half-life, greater binding affinity for fibrin, and better resistance to plasminogen activator inhibitor (PAI-1) than either native t-PA or alteplase.2 These features allow for the administration of Metalyse® as a single, 5-10 second intravenous bolus injection.1
Metalyse® molecule
What is the dosage of Metalyse®?
For acute ischaemic stroke (AIS), Metalyse® should be administered on the basis of body weight, with a maximum single dose of 5,000 units (25 mg Metalyse®). The required dose should be administered as a single intravenous bolus over approximately 5 to 10 seconds.1
The volume required to administer the correct total dose can be calculated from the following scheme:
| Patients' body weight category (kg) | Tenecteplase (U) | Tenecteplase (mg) | Corresponding volume of reconstituted solution (mL) |
|---|---|---|---|
| <60 | 3000 | 15.0 | 3.0 |
| ≥60 to <70 | 3500 | 17.5 | 3.5 |
| ≥70 to <80 | 4000 | 20.0 | 4.0 |
| ≥80 to <90 | 4500 | 22.5 | 4.5 |
| ≥90 | 5000 | 25.0 | 5.0 |
How is Metalyse® supplied?
For the treatment of acute ischaemic stroke, Metalyse® 5000 units (25mg) is supplied as a white to off-white powder containing 5,000 units (25 mg) of tenecteplase in a 10 ml clear glass vial, with a coated grey rubber stopper and a crimp cap.
Metalyse® 5000 units (25mg) should be reconstituted by adding 5 ml of sterile water for injection to the vial using a needle and a syringe (water, needle and syringe are not provided in the package).1
References
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Keyt BA et al. A faster-acting and more potent form of tissue plasminogen activator. Proc Natl Acad Sci USA. 1994;91(9):3670-3674. doi:10.1073/pnas.91.9.3670.