Class: Thrombin inhibitor
- Powder for injection, lyophilized 15 mg
Binds to thrombin, blocking the thrombogenic activity of thrombin, thereby prolonging the clotting time of human plasma. Activated partial thromboplastin time (aPTT) is a measure of the anticoagulant activity of desirudin.
Following subcutaneously administration of 0.3 or 0.5 mg/kg, absorption is complete. C max is reached 1 and 3 h after single subcutaneously doses of 0.1 to 0.75 mg/kg, respectively.
Binds directly to thrombin.
Metabolized and eliminated by the kidney with 40% to 50% excreted unchanged.
Mean terminal elimination t ½ is approximately 2 h.
Special PopulationsRenal Function Impairment
Elimination t ½ is prolonged in severe renal insufficiency up to 12 h. Dose adjustments are recommended in certain circumstances based on degree of impairment or aPTT measurements.Elderly
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Dosage adjustment in patients with moderate and severe renal function impairment is necessary.
Indications and Usage
Prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism, in patients undergoing elective hip replacement surgery.
Hypersensitivity to natural or recombinant hirudins; patients with active bleeding and/or irreversible coagulation disorders.
Dosage and AdministrationAdults
Subcutaneous 15 mg every 12 h with the initial dose given up to 5 to 15 min before surgery, but after induction of regional block anesthesia if used.Renal Function Impairment Moderate impairment (Ccr 31 to 60 mL/min/1.73 m 2 )
Initiate therapy at 5 mg every 12 h. If aPTT exceeds 2 times control, interrupt therapy until the value returns to less than 2 times control, then resume therapy at a reduced dose based on the initial degree of aPTT abnormality.Severe impairment (Ccr less than 31 mL/min/1.73 m 2 )
Initiate therapy at 1.7 mg every 12 h and monitor aPTT and serum creatinine at least daily. If aPTT exceeds 2 times control, interrupt therapy until the value returns to less than 2 times control; then consider further dose reductions based on the initial degree of aPTT abnormality.
- For subcutaneously administration only.
- Rotate injection sites between left and right anterolateral or posterolateral thigh or abdominal wall.
- Follow manufacturer's instructions for reconstitution of powder. Do not use any diluent other than that supplied with the powder.
- Desirudin cannot be used interchangeably with other hirudins.
Store unopened vials at controlled room temperature (59° to 86°F). Protect from light. Use reconstituted solution immediately if possible. Reconstituted solution may be stored for up to 24 h at room temperature and protected from light. Discard any unused solution or solution that has been stored for over 24 h.
Drug InteractionsAgents that enhance risk of hemorrhage (eg, anticoagulants, dextran 40, systemic glucocorticoids, thrombolytics)
Discontinue prior to initiation of desirudin therapy.
Do not mix with other injections, solvents, or infusions.
Laboratory Test Interactions
None well documented.
Thrombosis, hypotension, cerebrovascular disorder (less than 2%).
Nausea (2%); vomiting, hematemesis (less than 2%).
Hemorrhage (30%); hematomas (6%); injection site mass, wound secretion (4%); serious hemorrhage, anemia (3%); deep thrombophlebitis (2%); hypersensitivity, leg edema, fever, decreased hemoglobin, hematuria, dizziness, epistaxis, impaired healing (less than 2%); major hemorrhage (less than 1%, also reported rarely in postmarketing but sometimes fatal); anaphylactic/anaphylactoid (postmarketing).
Neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture in patients anticoagulated with selective inhibitors of thrombin, such as desirudin, may increase the risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. The risk of these events may be increased by use of indwelling spinal catheters for analgesia administration or by concurrent use of drugs affecting hemostasis (eg, nonsteroidal anti-inflammatory drugs, platelet inhibitors, or other anticoagulants). The risk appears to be increased by traumatic or repeated epidural or spinal puncture. Patients should be monitored frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.
Monitor patient for signs of bleeding throughout therapy.
Category C .
Safety and efficacy not established.
Use with caution because of increased likelihood of decreased renal function.
Use with caution, adjusting the dose as indicated.
Use with caution.
Antibodies have been reported in patients treated with hirudin. Do not exclude potential for cross-sensitivity to hirudin products.
Epidural spinal anesthesia/analgesia
If patient has concurrent epidural spinal anesthesia/analgesia, ensure catheter is placed prior to initiating desirudin therapy and is removed when the anticoagulant effect of desirudin is low. Frequently assess patient with epidural catheter for signs or symptoms of spinal hematoma (eg, midline back pain, numbness or weakness in lower extremities, bowel and/or bladder dysfunction).
Use with caution in patients with increased risk of hemorrhage (eg, recent major surgery, organ biopsy, or puncture of a noncompressible vessel within the last mo, history of hemorrhagic stroke, intracranial or intraocular bleeding, recent ischemic stroke, severe uncontrolled hypertension, bacterial endocarditis, known hemostatic disorder, history of GI or pulmonary bleeding within the past 3 mo).
Monitor aPTT daily in patients with increased risk of bleeding and/or renal function impairment. Monitor serum creatinine daily in patients with renal function impairment.
Switching from oral anticoagulants
Greater inhibition of hemostasis measured by aPTT, PT, and INR occurs. Monitor anticoagulant activity in evaluation of overall coagulation status of the patient during the switch.
- Advise patient, family, or caregiver that medication will be prepared and administered by a health care professional in a hospital setting.
- Instruct patient or family member to report any signs of bleeding or allergic reaction immediately.
- Instruct patient with epidural catheter to immediately report any of the following: midline back pain, numbness or weakness in lower extremities, bowel and/or bladder dysfunction.
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