Tenecteplase

Tenecteplase
Names
Trade namesTNKase, Metalyse, others
IUPAC name
  • Human tissue plasminogen activator
Clinical data
Drug classTissue plasminogen activator (tPA)[1]
Main usesST elevation myocardial infarction (STEMI), pulmonary embolism[1]
Side effectsBleeding[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Typical dose30 to 50 mg[1]
External links
AHFS/Drugs.comMonograph
Legal
License data
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetics
ExcretionLiver
Chemical and physical data
FormulaC2561H3919N747O781S40
Molar mass58951.37 g·mol−1

Tenecteplase (TNK), sold under the trade names TNKase among others, is a medication used to treat ST elevation myocardial infarction or pulmonary embolism with low blood pressure.[1][3] It may also be used for stroke.[3] It is given by injection into a vein.[1]

Common side effects include bleeding such as nosebleeds, gastrointestinal bleeding, bruising, or blood in the urine.[1][2] It should not be used by those with anaphylaxis to gentamicin.[2] It is a tissue plasminogen activator (tPA) produced by recombinant DNA technology.[1] It works by dissolving blood clots.[2]

Tenecteplase was approved for medical use in the United States in 2000 and Europe in 2001.[1][2] In the United Kingdom it costs the NHS about £600 per dose as of 2021.[4] This amount in the United States costs about 6,500 USD.[5]

Medical uses

It is most commonly used for ST elevation myocardial infarction.[1] It may also be used for pulmonary embolism with low blood pressure and to treat stroke.[3][1]

The American Heart Association/American Stroke Association 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke supports considering tenecteplase over alteplase in people without contraindication to intravenous thrombolytics.[6]

Dosage

For STEMI the typical dose is 30 to 50 mg.[1] It is given over 5 to 10 seconds.[1][2] A similar dose may be used is massive pulmonary embolism.[7]

The amount of 10,000 units is equal to 50 mg.[8]

Mechanism of action

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.

Pharmacokinetics

Distribution: approximates plasma volume

Metabolism: Primarily hepatic

Half-life elimination: Biphasic: Initial: 20–24 minutes; Terminal: 90–130 minutes

Excretion: Clearance: Plasma: 99-119 mL/minute

  • Here is TNK-tPA. It is very similar to t-PA, but the glycosylation occurring in Kringle 1 is manipulated. The mutation T103N means that glycosylation occurs at that point. The mutation N117E means that the high mannose sugar residue is absent at that point
    Here is TNK-tPA. It is very similar to t-PA, but the glycosylation occurring in Kringle 1 is manipulated. The mutation T103N means that glycosylation occurs at that point. The mutation N117E means that the high mannose sugar residue is absent at that point
  • In human t-PA, the amino acids at position 296-299 are Lysine, Histidine, and two Arginines.
    In human t-PA, the amino acids at position 296-299 are Lysine, Histidine, and two Arginines.
  • In TNK-tPA, these amino acids have been replaced by four Alanines. This mutation is responsible for increased resistance to PAI-1.
    In TNK-tPA, these amino acids have been replaced by four Alanines. This mutation is responsible for increased resistance to PAI-1.

Manufacture

It is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line (Chinese hamster ovary cells). Tenecteplase is a 527 amino acid glycoprotein developed by introducing the following modifications to the complementary DNA (cDNA) for natural human tPA: a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 "Tenecteplase Monograph for Professionals". Drugs.com. Archived from the original on 15 August 2019. Retrieved 19 September 2021.
  2. 1 2 3 4 5 6 "Metalyse". Archived from the original on 11 November 2020. Retrieved 19 September 2021.
  3. 1 2 3 Burgos, Adrian M.; Saver, Jeffrey L. (August 2019). "Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke: Meta-Analysis of 5 Randomized Trials". Stroke. 50 (8): 2156–2162. doi:10.1161/STROKEAHA.119.025080.
  4. ↑ BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 231. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
  5. ↑ "TNKase Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 19 January 2021. Retrieved 19 September 2021.
  6. ↑ "Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association". www.ahajournals.org. doi:10.1161/str.0000000000000211. Archived from the original on 2020-11-22. Retrieved 2021-05-13.
  7. ↑ Martin, C; Sobolewski, K; Bridgeman, P; Boutsikaris, D (December 2016). "Systemic Thrombolysis for Pulmonary Embolism: A Review". P & T : a peer-reviewed journal for formulary management. 41 (12): 770–775. PMID 27990080.
  8. ↑ "Metalyse 10,000 units - Summary of Product Characteristics (SmPC) - (emc)". www.medicines.org.uk. Archived from the original on 2 March 2021. Retrieved 19 September 2021.
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