Peptide education
Desirudin
Iprivask · Revasc · CGP 39393
Desirudin is a recombinant hirudin anticoagulant that blocks thrombin, an enzyme involved in blood clotting. The US Iprivask label described its use to prevent deep vein thrombosis after elective hip replacement. FDA lists Iprivask as discontinued and its license as voluntarily revoked.
In one hip-replacement trial, confirmed deep vein thrombosis occurred in 13 of 174 evaluable patients assigned desirudin and 41 of 177 assigned unfractionated heparin. The analysis included patients with an adequate venogram or a confirmed event.
Overview
Quick answer
The hip-replacement studies tested desirudin to prevent clots around surgery, not to treat a clot that had already formed. FDA separately lists the product's marketing status as discontinued and its license as voluntarily revoked.
What is desirudin?
A 65-amino-acid recombinant hirudin that directly inhibits circulating and clot-bound thrombin. Iprivask was supplied for subcutaneous injection.
What did the US label cover?
Prevention of deep vein thrombosis, which can lead to pulmonary embolism, in people undergoing elective hip replacement surgery.
Is Iprivask still marketed in the United States?
FDA's Purple Book lists Iprivask as discontinued and its license as voluntarily revoked.
What was the label dose?
The archived label described 15 mg by subcutaneous injection every 12 hours, beginning shortly before hip surgery. It specified lower starting doses for moderate or severe kidney impairment, with kidney and clotting-test monitoring.
Why does the anesthesia plan matter?
The label carried a boxed warning that spinal or epidural bleeding associated with neuraxial anesthesia or spinal puncture could cause lasting paralysis.
Evidence
Evidence snapshot
The archived US indication was prevention of deep vein thrombosis in people undergoing elective hip replacement.
FDA lists the named Iprivask product as discontinued and its license as voluntarily revoked.
Confirmed deep vein thrombosis was less frequent with desirudin than with unfractionated heparin among patients included in the trial's efficacy analysis.
In another hip-replacement trial, the primary analysis found a major thromboembolic event in 39 of 802 patients given desirudin versus 60 of 785 given enoxaparin. The endpoint included proximal deep vein thrombosis, pulmonary embolism, or unexplained death.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Desirudin was studied for clot prevention after hip replacement. | Randomized trials compared perioperative desirudin with unfractionated heparin or enoxaparin after primary hip replacement. | Desirudin directly inhibits thrombin, including thrombin bound to a clot. | The clinical evidence concerns prevention in the surgical populations studied. |
| A lower clot rate means there is no bleeding risk. | The archived label warns of hemorrhage and spinal or epidural hematoma. The heparin-comparison trial found no statistically significant difference in its bleeding measures, which does not establish equal risk in every patient. | Bleeding remains a central safety concern. | |
| Kidney function is irrelevant to desirudin dosing. | The archived label specified reduced doses and daily aPTT and creatinine monitoring for moderate or severe renal impairment. | Kidney function affected both dose and monitoring in the label. |
Bottom line
Main takeaway
Desirudin was used to reduce clot risk after hip replacement, but it also increases bleeding risk.
FDA lists Iprivask as discontinued; its archived label describes the former US product.
The heparin trial's clot comparison used an evaluable subset of the randomized surgical population.
Identity
What it is
Desirudin is a recombinant hirudin analog. It binds thrombin directly and was administered by subcutaneous injection in hip-replacement trials.
The US label described prevention of deep vein thrombosis after elective hip replacement. FDA's product listing identifies Iprivask as discontinued.
Use context
Routes, doses, and cycle patterns
The archived Iprivask label described twice-daily subcutaneous dosing around elective hip surgery, with lower doses for moderate or severe kidney impairment.
Human studies and product labels
Archived Iprivask label
- Purpose
- Prevent deep vein thrombosis after elective hip replacement
- Context
- Historical US prescribing information
- Route
- Subcutaneous
- Amount
- 15 mg
- Frequency
- Every 12 hours
- Duration
- Up to 12 days was described in controlled trials
The label placed the first dose shortly before surgery and after regional block anesthesia if used. For creatinine clearance of 31 to 60 mL/min per 1.73 m2, the label specified a starting dose of 5 mg every 12 hours; below 31, it specified 1.7 mg every 12 hours. It called for at least daily aPTT and creatinine monitoring for these patients. The renal-dose table did not specify an automatic starting-dose reduction for mild impairment; aPTT results could still prompt adjustment.
Hip-replacement trial versus unfractionated heparin
- Purpose
- Prevent postoperative thromboembolism
- Context
- Randomized double-blind clinical trial
- Route
- Subcutaneous
- Amount
- 15 mg desirudin
- Frequency
- Twice daily, starting before surgery
- Duration
- 8 to 11 days
The comparison group received 5,000 IU unfractionated heparin three times daily.
Hip-replacement trial versus enoxaparin
- Purpose
- Prevent postoperative thromboembolism
- Context
- Randomized double-blind clinical trial
- Route
- Subcutaneous
- Amount
- 15 mg desirudin
- Frequency
- Twice daily
- Duration
- 8 to 12 days
The comparator was enoxaparin 40 mg once daily. Renal impairment was listed as a screening exclusion, but a later analysis identified reduced kidney function among participants.
Research
Research evidence
Randomized hip-replacement trials compared desirudin with two heparin regimens. Their outcomes were measured during a defined postoperative period and do not establish how treatment choices compare in other surgical settings.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Desirudin versus unfractionated heparin | 445 randomized patients having elective primary total hip replacement | Double-blind randomized comparison | Desirudin twice daily versus unfractionated heparin three times daily | Confirmed deep vein thrombosis occurred in 13 of 174 versus 41 of 177 evaluable patients. | The efficacy analysis included 351 patients with evaluable venograms or a confirmed event. | Strong for the measured surgical outcome |
| Desirudin versus enoxaparin | 2,079 randomized patients having primary total hip replacement; 1,587 included in the primary efficacy analysis | Double-blind randomized comparison | Desirudin 15 mg twice daily versus enoxaparin 40 mg once daily | Major thromboembolic events occurred in 39 of 802 patients given desirudin versus 60 of 785 given enoxaparin. The endpoint included proximal deep vein thrombosis, pulmonary embolism, or unexplained death. | The trial listed renal impairment as a screening exclusion. A later post-hoc analysis classified 577 of 2,078 treated participants as having stage 3B kidney disease or worse. Patients without adequate outcome assessment were excluded from the primary efficacy analysis. | Strong for the measured surgical outcome |
Cautions
Safety and unknowns
- The archived label warned of bleeding and carried a boxed warning for spinal or epidural hematoma in patients receiving neuraxial anesthesia or spinal puncture.
- Moderate or severe kidney impairment can increase the anticoagulant effect. The label specified lower starting doses with at least daily aPTT and creatinine monitoring for those patients. It also called for daily monitoring in patients with renal impairment generally; further dose changes depended on aPTT.
- The label contraindicated use with active bleeding, irreversible coagulation disorders, or known hypersensitivity to natural or recombinant hirudins.
Mechanism
How it is proposed to work
Desirudin inhibits thrombin, an enzyme that helps form and stabilize blood clots.
It inhibits both circulating and clot-bound thrombin and prolongs clotting tests such as aPTT.
Details
Technical details
Sources
References
- 1.
FDA. Iprivask prescribing information archived by FDA
Archived US indication, dosing, renal adjustments, and boxed warning; product marketing status is described separately.
- 2.
FDA Purple Book. FDA Purple Book listing for Iprivask
FDA lists Iprivask as discontinued and its license as voluntarily revoked.
- 3.
doi:10.2106/00004623-199703000-00002 PMID:9070519
Randomized double-blind hip-replacement comparison with unfractionated heparin.
- 4.
PubMed. A comparison of recombinant hirudin with a low-molecular-weight heparin after total hip replacement
doi:10.1056/NEJM199711063371901 PMID:9358126
Randomized hip-replacement comparison with enoxaparin.
- 5.
doi:10.1111/j.1538-7836.2012.04803.x PMID:22672318
Post-hoc kidney-function analysis of the desirudin versus enoxaparin hip-replacement trial.