Tenecteplase (TNK-tPA)
Aka. TNK-tPA, Metalyse, TNKase, Elaxim
CLASS
- Thrombolytic
INDICATIONS
- Acute STEMI
- Acute Ischaemic stroke
- Acute massive pulmonary embolism
- Including Cardiac arrest due to suspected PE
- Central venous catheter occlusion
ADMINISTRATION / DOSING
- Intravenous (IV)
- Adults:
- Acute STEMI (halve the dose if >75 y/o):
- <60 kg: 30 mg (6000 units)
- 60 – <70 kg: 35 mg (7000 units)
- 70 – <80 kg: 40 mg (8000 units)
- 80 – <90 kg: 45 mg (9000 units)
- ≥90 kg: 50 mg (10 000 units)
- Acute massive PE / Cardiac arrest with suspected PE:
- As above
- Acute Ischaemic stroke (off-label use but is recommended as part of Stroke Foundation Guideline):
- 0.25 mg/kg as a single bolus, give within 4.5 h of symptom onset (MAX dose 25 mg)
- Central venous catheter occlusion
- >30 kg: 2 mg in 2 mL into the occluded catheter, consider second dose 120 mins later
- <30kg: dose equal to 110% of catheter lumen volume, MAX 2 mg in 2mg
- Acute STEMI (halve the dose if >75 y/o):
- Children:
- Refer to paediatric guidelines
- Administration-specific things:
- Precipitates in 5% dextrose, must be drawn up in water for injection or 0.9% sodium chloride
- It comes in a set-up not-unlike Prothrombinex with a diluent and a transfer device. Don’t shake it up, swirl gently.
MECHANISM OF ACTION
- It is a tissue plasminogen activator (tPA)
- It enhances the conversion of plasminogen to plasmin by binding to fibrin initiating fibrinolysis with limited systemic proteolysis.
- The circulating plasminogen that has been activated will cause a systemic lytic state
- Tenecteplase requires fibrin as a cofactor for the activation of plasminogen
- Tenecteplase results in a decrease of plasminogen and fibrinogen levels 50% lower than those of alteplase (at ~25%)
PHARMACEUTICS
- It is a genetically engineered variant of alteplase with resulting:
- Increase in plasma half-life
- Enhanced fibrin specificity
- Increased resistance to inactivation by plasminogen activator inhibitor 1 (PAI-1)
- Excipients:
- Arginine, phosphoric acid and polysorbate 20
- White lyophilised powder for reconstitution
- Store below 30oC before use
- When reconstituted it is a colourless to pale yellow transparent solution with a pH of 7.3 and osmolality of 215 mOsm/kg
- Comes with preservative-free sterile water for injection with a transfer device
- Once reconstituted, it must be kept between 2 – 8oC and then used within 8 hours
PHARMACOKINETICS
- Absorption
- Initial response: ~11 mins
- Peak plasma: at the end of the bolus
- Distribution
- Volume of distribution: ~6 L
- Metabolism
- Presumed liver – degraded to constituent amino acids (based on alteplase)
- Minor plasma – inactivated by PAI-1
- Elimination
- Total body clearance: 99 -119 mL/min
- Parent compound cleared in 20 – 24 mins
- Initial plasma half-life 22 mins, biphasic terminal T1/2 115 mins
PHARMACODYNAMICS
- CNS
- Post-lysis cerebral oedema in the infarcted zone
- CVS
- Transient drop in blood pressure during administration
- Arrhythmias with reperfusion after lysis for a myocardial infarction
- RESP
- Bronchospasm
- OTHER
- Massive haemorrhage
CONTRAINDICATIONS
RELATIVE
- Everything is a relative contraindication when you’re doing CPR on someone with a massive PE…
- Age >80 review risk vs benefits given the increased risk of ICH
ABSOLUTE
- Known hypersensitivity/anaphylaxis reactions to the medication or related excipients (increased risk with ACEi use)
- Active internal bleeding
- Current intracranial haemorrhage
- Intracranial neoplasm, arteriovenous malformation, aneurysm, or other conditions that may increase haemorrhage
- Bleeding diathesis (e.g. von Willebrand disease, haemophilia, advanced liver disease etc.)
- Recent (i.e. within 3 months) intracranial or intraspinal surgery, major surgery
- Recent (i.e. within 3 months) serious head trauma
- Recent (i.e. within 3 months) stroke, for patients with acute myocardial infarction or pulmonary embolism
- Severe uncontrolled hypertension
- Subarachnoid haemorrhage
- Active peptic ulcer disease
- Prolonged CPR
IN ACUTE ISCHAEMIC STROKE
In addition to the above:
- Symptoms began >4.5 hours prior to infusion start, or when time onset is unknown (or >9 hours in specific circumstances, see Stroke Foundation Guidelines)
- Seizure
- Platelets <100
- Already anticoagulated
- Rapid resolution of symptoms or only minor neurological deficit
- SBP >185 / SBP >110
- Blood glucose <2.8 mmol or >22.2 mmol/L
- Patients < 18 years
- History of prior stroke and Diabetes Mellitus
- Severe stroke as assessed by NIHSS >25 or imaging techniques as higher risk of ICH
IN ACUTE MYOCARDIAL INFARCTION
In addition to the above:
- Ischaemic stroke or TIA in the preceding 6 months, except a current stroke with onset of < 4.5 hours
RISKS
- Reperfusion arrhythmias (in myocardial infarction) – 10%
- Severe haemorrhage 1.8%
- Moderate haemorrhage ~10% (requiring transfusion, but not hemodynamically compromising)
- Gastrointestinal haemorrhage – ~5%
- Intracranial haemorrhage – ~0.5-2% (increases to ~4% for >75 y/o patients)
- With ~25-50% of those ICH being fatal
- Orolingual angioedema (increased risk with ACEi use): 1-8%
- Rare:
- Anaphylaxis
- Seizure
- Dysphagia
- Retroperitoneal haemorrhage
REVERSAL
EVIDENCE
- See STEMI Management
- See Stroke Thrombolysis
- See Pulmonary Embolism
- Briefly: Associated with reduced pulmonary artery pressure, and faster reduction in thrombus size
References and Links
CCC Pharmacology Series
Respiratory: Bosentan, Delivery of B2 Agonists in Intubated Patients, Nitric Oxide, Oxygen, Prostacyclin, Sildenafil
Cardiovascular: Adenosine, Adrenaline (Epinephrine), Amiodarone, Classification of Vasoactive drugs, Clevidipine, Digoxin, Dobutamine, Dopamine, Levosimendan, Levosimendan vs Dobutamine, Milrinone, Noradrenaline, Phenylephrine, Sodium Nitroprusside (SNiP), Sotalol, Vasopressin
Neurological: Dexmedetomidine, Ketamine, Levetiracetam, Lignocaine, Lithium, Midazolam, Physostigmine, Propofol, Sodium Valproate, Sugammadex, Thiopentone
Endocrine: Desmopressin, Glucagon Therapy, Medications and Thyroid Function
Gastrointestinal: Octreotide, Omeprazole, Ranitidine, Sucralfate, Terlipressin
Genitourinary: Furosemide, Mannitol, Spironolactone
Haematological: Activated Protein C, Alteplase, Aprotinin, Aspirin, Clopidogrel, Dipyridamole, DOACs, Factor VIIa, Heparin, LMW Heparin, Protamine, Prothrombinex, Tenecteplase, Tirofiban, Tranexamic Acid (TXA), Warfarin
Antimicrobial: Antimicrobial Dosing and Kill Characteristics, Benzylpenicillin, Ceftriaxone, Ciprofloxacin, Co-trimoxazole / Bactrim, Fluconazole, Gentamicin, Imipenem, Linezolid, Meropenem, Piperacillin-Tazobactam, Rifampicin, Vancomycin
Analgesic: Alfentanil, Celecoxib, COX II Inhibitors, Ketamine, Lignocaine, Morphine, NSAIDs, Opioids, Paracetamol (Acetaminophen), Paracetamol in Critical Illness, Tramadol
Miscellaneous: Activated Charcoal, Adverse Drug Reactions, Alkali Therapies, Drug Absorption in Critical Illness, Drug Infusion Doses, Epidural Complications, Epidural vs Opioids in Rib Fractures, Magnesium, Methylene Blue, Pharmacology and Critical Illness, PK and Obesity, PK and ECMO, Sodium Bicarbonate Use, Statins in Critical Illness, Therapeutic Drug Monitoring, Weights in Pharmacology
Toxicology: Digibind, Flumazenil, Glucagon Therapy, Intralipid, N-Acetylcysteine, Naloxone, Propofol Infusion Syndrome
- Australian Injectable Drugs Handbook, 8th Edition. (2023). Retrieved 28 April 2023, from https://aidh.hcn.com.au/
- Australian Medicines Handbook. (2023). Retrieved 28 April 2023 from https://amhonline.amh.net.au/
- IBM Micromedex. (2023). Retrieved 28 April 2023, from https://www.micromedexsolutions.com
- MIMS Online. (2023). Retrieved 28 April 2023, from https://www.mimsonline.com.au
- Stroke Foundation. (2022). Clinical Guidelines for Stroke Management. Living Clinical Guidelines for Stroke Management. https://informme.org.au/guidelines/living-clinical-guidelines-for-stroke-management
FOAMED
- Resus Review — TPA mixing tutorial (2013)
LITFL
- Drugs for cardiac arrest
- Haemorrhage post-thrombolysis
- Pharm 101: Thrombolytic Agents
- STEMI management
- Thrombolytic Agents
- Thrombolysis for PE
- Thrombolysis for Stroke
- A three-part series into the use of thrombolysis in stroke
Critical Care
Compendium
ICU Advanced Trainee BMedSci [UoN], BMed [UoN], MMed(CritCare) [USyd] from a broadacre farm who found himself in a quaternary metropolitan ICU. Always trying to make medical education more interesting and appropriately targeted; pre-hospital and retrieval curious; passionate about equitable access to healthcare; looking forward to a future life in regional Australia. Student of LITFL.
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.
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