#Antidote for heparin plus#

MedWire (is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. Do not add heparin to infusion lines of other drugs, and do not piggyback other drugs into heparin line. Protamine sulfate, a derivative of fish sperm, is commonly used for the reversal of anticoagulation effect of unfractionated heparin (UFH) and low-molecular. Large-scale production processes are required before clinical trials can be carried out. However, they note that at present, the antithrombin variant can only be produced on a small scale. 'These results clearly demonstrate that AT-N135Q-Pro394 can reverse the anticoagulant activity of fondaparinux and thus could be used as an antidote for this drug ,' write the researchers in the journal Blood. The researchers observed a similar antidote effect in vivo, as administration of AT-N135Q-Pro394 to mice treated with fondaparinux at five times the curative dose neutralized 86% of the anti-Xa activity within 5 minutes. In additon, AT-N135Q-Pro394 decreased UFH and LMWH anticoagulant activity by 76% in overdosed plasma, indicating that it acts as a potent antidote to all heparin-like anticoagulants. Moreover, the antidote effect was dose-dependant. They found that AT-N135Q-Pro394, at a concentration equal to the endogenous plasma antithrombin concentration, significantly reduced the fondaparinux concentration from 3.0 to 1.23 mg/l - a concentration equivalent to that used for curative treatment. There are potential alternatives in the pipeline currently being investigated in pre-clinical studies.To test the antidote's ability to reverse fondaparinux overdose, they added increasing concentrations of AT-N135Q-Pro394 to plasma spiked with approximately three times the maximal curative dose of fondaparinux. Substitutions for the heparin/protamine combination such as bivalirudin should be considered in appropriate procedures due to lack of protamine alternatives. Unfortunately, there are no alternatives readily available for use in the occurrence of a protamine shortage. Protamine remains as the only reversal agent for unfractionated heparin. The pegnivacogin/anivamersen combination along with FIXa aptamer antidote pair are promising alternatives currently in the pipeline for patients undergoing cardiac surgery. Bivalirudin is currently available as an anticoagulant and eliminates the need for an antidote, due to its short half-life of 25 minutes. It is specifically used in heparin overdose, in low molecular weight heparin. With no promising leads, alternatives to the heparin and protamine combination were also considered. Protamine sulfate is a medication that is used to reverse the effects of heparin.

#Antidote for heparin plus#

Of the agents listed, the following are currently under investigation in pre-clinical studies: heparinase, UHRA, riAT, Dex40-GTMAC3, HRG plus zinc, quaternized chitosan derivative, and LMWP. Based on the available literature, the following compounds have been investigated as alternatives: hexadimethrine bromide, heparinase, platelet factor 4 (PF4), heparin removal devices, synthetic protamine variants, methylene blue, vancomycin, tolonium chloride, ciraparantag, universal heparin reversal agent (UHRA), Dex40-GTMAC3, histidine-rich glycoprotein (HRG) plus zinc, and recombinant inactive antithrombin (riAT), low molecular weight protamine (LMWP), quaternized chitosan derivative. Results:Ĭurrently, there is no FDA approved alternative to protamine however, multiple products have been considered for potential use. A literature search was conducted during the month of July 2019 in Medline, Embase, and International Pharmaceutical Abstracts using the following search terms: “heparin,” “antidote,” “protamine,” 'cardiopulmonary bypass,” “reversal,” “unfractionated heparin,” and ''alternative.” Studies evaluating possible alternatives for the reversal of protamine were included in this review. Methods: An inquiry was submitted to the Christy Houston Drug Information Center (DIC) at the Belmont University College of Pharmacy in July 2019 regarding alternatives to protamine for unfractionated heparin reversal during a protamine shortage. This literature review provides currently available alternatives for protamine when the use of unfractionated heparin is unavoidable. Use of protamine alone produces a weak anticoagulation effect but when used in combination with heparin, a strong acid, a salt is formed which neutralizes the compound’s activity. Protamine is the only FDA approved reversal agent for heparin.

An evidence based approach for managing drug shortages allows clinicians to provide safe and effective patient care. Purpose: A recent possibility of protamine shortage prompted an inquiry for available alternatives for unfractionated heparin reversal. 2019 Midyear Clinical Meeting Skip to main content