Desirudin

A 65-amino-acid recombinant hirudin (desulfato-hirudin) and subcutaneous direct thrombin inhibitor approved by the FDA as Iprivask in 2003 for deep-vein thrombosis prophylaxis after hip replacement; the product was later discontinued in the United States.

Also referenced as: Iprivask, Revasc, CGP 39393, CGP-39393, desulfato-hirudin

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What is Desirudin?

Desirudin is a small protein rather than a short peptide: a 65-amino-acid recombinant form of hirudin, the thrombin inhibitor secreted by the salivary glands of the medicinal leech Hirudo medicinalis, produced in Saccharomyces cerevisiae with three disulfide bridges and a molecular weight of about 6,964 Da. It is identical in sequence to natural hirudin variant 1 but lacks the sulfate group on tyrosine 63, hence the chemical name desulfato-hirudin (and the development code CGP 39393 from Ciba-Geigy). It was authorized in the European Union as Revasc on July 9, 1997 and approved by the FDA as Iprivask on April 4, 2003 for prophylaxis of deep-vein thrombosis in patients undergoing elective hip replacement surgery, making it the first subcutaneous direct thrombin inhibitor approved in the United States. Desirudin is a hospital anticoagulant that is no longer marketed in either region; it appears in peptide discussions as the parent molecule of the hirudin family, alongside bivalirudin, a synthetic 20-residue peptide built by joining an active-site-directed tetrapeptide to hirudin’s C-terminal dodecapeptide, and it has essentially no footprint as a research-market peptide.

How it works

• Bivalent, essentially irreversible thrombin binding. The compact N-terminal domain of hirudin inserts into the active-site cleft of thrombin while the extended, acidic C-terminal tail wraps along anion-binding exosite I, the surface thrombin uses to recognize fibrinogen; in the 2.3 Å crystal structure of the complex, 27 of the 65 hirudin residues contact thrombin through 10 ion pairs and 23 hydrogen bonds (Rydel et al., Science, 1990, 249(4966):277–280).
• Femtomolar affinity and strict specificity. Hirudin inhibits thrombin with a dissociation constant of about 20 fM at an ionic strength of 0.125, with the constant rising about 20-fold as ionic strength increases from 0.1 to 0.4 (Stone and Hofsteenge, Biochemistry, 1986, 25(16):4622–4628). Inhibition requires no antithrombin III cofactor, and desirudin has no meaningful activity against other coagulation serine proteases. One molecule of desirudin binds one molecule of thrombin, and because the interaction is independent of antithrombin and heparin-binding sites, it reaches both free circulating and clot-bound thrombin (FDA label).
• Renal elimination and a short half-life. The terminal half-life is about 2 to 3 hours after intravenous dosing and about 2 hours after subcutaneous dosing, with 40 to 50% of a dose excreted unchanged in urine; total clearance falls in proportion to creatinine clearance, and dose-normalized exposure rose about 2.8-fold in moderate and 7-fold in severe renal impairment in a dedicated pharmacokinetic study (Lefèvre et al., Clinical Pharmacology and Therapeutics, 1997, 62(1):50–59).
• No interaction with the heparin–platelet factor 4 axis. Desirudin is structurally unrelated to heparin and does not bind platelet factor 4, so it does not itself induce the antibodies that cause heparin-induced thrombocytopenia; in a randomized cardiothoracic-surgery study in which most patients also received intraoperative heparin, new PF4/heparin antibodies appeared in 10.2% of desirudin and 13.6% of heparin patients, and in none of the 36 desirudin-treated patients who had no heparin exposure (Avidan et al., Thrombosis Research, 2011, 128(6):524–529).

Research status

Desirudin’s evidence base is concentrated in European hip-replacement trials from the 1990s, supplemented by small US studies run after 2010. There is no active clinical development.

• Dose-ranging trial versus unfractionated heparin. Eriksson et al. (1996), Lancet 347(9002):635–639, was a double-blind multicenter European study of 1,119 elective hip-replacement patients randomized to CGP 39393 at three dose levels or unfractionated heparin for 8 to 11 days. Venographic deep-vein thrombosis occurred in 34.2% of heparin patients versus 23.9%, 18.4%, and 17.7% across the ascending desirudin groups, establishing the 15 mg twice-daily regimen taken forward.
• Confirmatory trial versus unfractionated heparin. Eriksson et al. (1997), Journal of Bone and Joint Surgery (American) 79(3):326–333, randomized 445 patients; in the per-protocol analysis, confirmed deep-vein thrombosis occurred in 7% of 174 desirudin patients versus 23% of 177 heparin patients, with no significant difference in bleeding. The FDA label reports total venous thromboembolism of 5.8% versus 19.1% in the intent-to-treat population of this study.
• Pivotal trial versus enoxaparin. Eriksson et al. (1997), New England Journal of Medicine 337(19):1329–1335, randomized 2,079 patients at 31 centers in 10 European countries, double-blind, to desirudin started within 30 minutes before surgery or enoxaparin 40 mg started the evening before, for 8 to 12 days; 1,587 were evaluable for efficacy. Proximal deep-vein thrombosis was 4.5% versus 7.5% (P = 0.01, a 40.3% relative reduction) and overall deep-vein thrombosis 18.4% versus 25.5% (P = 0.001), with similar safety profiles. This trial was the basis of both the European and US approvals. A Cochrane review later pooled direct thrombin inhibitors against low-molecular-weight heparins and vitamin K antagonists after hip or knee replacement: the class was as effective for major venous thromboembolism, but total bleeding after hip replacement was higher than with low-molecular-weight heparin (an excess the authors attributed to ximelagatran and dabigatran rather than desirudin) and all-cause mortality was higher in the direct-thrombin-inhibitor group (Salazar et al., Cochrane Database of Systematic Reviews, 2010, CD005981).
• Immunogenicity. Greinacher et al. (2003), Blood 101(7):2617–2619, found that among 112 patients from the dose-finding hip-surgery study, 11 (9.8%) developed IgG anti-hirudin antibodies, a rate not significantly different from that seen with lepirudin in heparin-induced thrombocytopenia; antibodies had no measurable effect on drug levels, thrombosis, bleeding, or allergic reactions in this small series, but the authors could not exclude rare severe effects.
• Heparin-induced thrombocytopenia. The only randomized data are the PREVENT-HIT pilot (NCT00787332; Boyce et al., American Journal of Therapeutics, 2011, 18(1):14–22), an open-label US comparison of fixed-dose subcutaneous desirudin with aPTT-adjusted intravenous argatroban in suspected HIT with or without thrombosis. It was terminated for low enrollment after 16 patients (8 naive to direct thrombin inhibitors and 8 already on argatroban); there were no major bleeds on desirudin versus two on argatroban, and one minor bleed in each arm. The trial is too small to support any efficacy claim, and desirudin was never labeled for HIT; the hirudin that carried a HIT indication was lepirudin (Refludan), a different recombinant variant discontinued in 2012.
• Broader prophylaxis populations. DESIR-ABLE (NCT00913133; Bergese et al., Clinical and Applied Thrombosis/Hemostasis, 2013, 19(4):418–423) was a phase 4, single-arm, open-label study of 516 hospitalized surgical and medically ill patients at 19 US centers receiving desirudin for thrombosis prophylaxis, 292 of whom had creatinine clearance below 60 mL/min; there were no major bleeds and no VTE-related deaths. A case series of total knee arthroplasty patients from the same program was reported separately (Jove et al., American Journal of Therapeutics, 2014, 21(6):496–499). The 120-patient randomized cardiothoracic-surgery study (NCT00329433; Avidan et al., 2011) found deep-vein thrombosis in 4.9% of desirudin and 3.4% of heparin patients with two bleeding events per group.
• Regulatory record. Revasc’s EU authorization was withdrawn by the European Commission on July 18, 2014 at the holder’s request; the EMA record notes that the product was not marketed in any European country. In the United States, the application changed holders before the product was discontinued; the final labeling supplement was approved on May 18, 2015. As of November 2026, Drugs@FDA lists application 021271 (deemed a biologics license application on March 23, 2020) with Discontinued marketing status, no desirudin product appears in the NDC directory or on DailyMed, and no notice withdrawing the approval has been published. No new desirudin trials have been registered on ClinicalTrials.gov since 2009, and no approval, generic, or biosimilar activity was identified for 2025 or 2026.

Common dosage forms

• Single-dose vial with diluent. A single-dose vial of 15.75 mg lyophilized desirudin with diluent, for subcutaneous use; this was the Iprivask presentation in the United States.
• Revasc. The same 15 mg lyophilized vial presentation with a separate diluent, the European Union presentation.
• No other forms. Desirudin has never been marketed as an intravenous premix, oral, nasal, or depot product.

Key considerations

• Regulatory status. The FDA Approved status reflects the April 4, 2003 approval of Iprivask (application 021271) for deep vein thrombosis prophylaxis after hip replacement. The product was discontinued in the United States and Drugs@FDA lists it as Discontinued; the application was deemed a biologics license in March 2020 and has not been withdrawn.
• A narrow, dated evidence base. The pivotal trials enrolled hip-replacement patients in the 1990s against unfractionated heparin and enoxaparin; desirudin was never compared with fondaparinux or the direct oral anticoagulants that now dominate orthopedic prophylaxis, and the later US studies were small, open-label, or single-arm. The HIT evidence consists of a terminated 16-patient pilot, and desirudin never carried a HIT indication.
• Bleeding, renal accumulation, and immunogenicity. Any hemorrhage occurred in about 30% of desirudin-treated patients in the hip-replacement trials (22% with heparin, 33% with enoxaparin), with serious hemorrhage in about 3%, and because 40 to 50% of a dose is cleared unchanged by the kidney, exposure rises steeply as creatinine clearance falls with no reversal agent. Roughly 10% of patients form anti-hirudin antibodies after a single prophylactic course, which can prolong the anticoagulant effect, and the label’s principal warnings concerned bleeding with neuraxial anesthesia and hypersensitivity to hirudins.
• Naming. Desirudin, desulfato-hirudin, CGP 39393, Iprivask, and Revasc are the same molecule. It should not be confused with lepirudin (Refludan), a different 65-residue recombinant hirudin variant with leucine at position 1 and threonine at position 2 that was approved for HIT and discontinued in 2012, nor with bivalirudin (Angiomax), a 20-residue synthetic peptide that borrows only hirudin’s C-terminal tail, nor with the small-molecule direct thrombin inhibitors argatroban and dabigatran.