Reteplase (Retavase®) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific).

Reteplase can be administered as a bolus dose (nonweight-based) rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival.

In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke.

Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other thrombolytic agents.

With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.

Reteplase, a single-chain, nonglycosylated peptide, is a fibrin-specific recombinant plasminogen activator that contains the kringle 2 and protease domains of native t-PA, but lacks the kringle 1, fibronectin finger, and epidermal growth factor domains. It exerts its thrombolytic action by catalyzing the conversion of the inactive proenzyme plasminogen to the active protease plasmin, which degrades the fibrin matrix of the thrombus. Reteplase has a fibrin-specific activity and, in animal models of thrombosis, is a more potent thrombolytic than alteplase, and produces reperfusion significantly faster than alteplase, streptokinase, or urokinase. In patients with acute myocardial infarction (AMI), reteplase decreased levels of fibrinogen, plasminogen, and α₂-antiplasmin. In these patients, a double-bolus (10U + 10U; 30 minutes apart) dose of reteplase produced relatively greater alterations in hemostatic variables than a single bolus (10U) dose. A paradoxical activation of the coagulation system seen after reteplase treatment is blunted in a beneficial fashion when reduced-dose reteplase is combined with abciximab in AMI patients.

Pharmacokinetic studies in healthy volunteers have suggested that not all of the reteplase antigen in plasma was active. In healthy volunteers, the apparent volume of distribution of reteplase …