Boxed Warning
Spinal/Epidural hematoma:
When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with selective inhibitors of thrombin such as desirudin may be at 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 the use of indwelling spinal catheters for administration of analgesia or by the concomitant use of drugs affecting hemostasis such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants. Likewise with such agents, the risk appears to be increased by traumatic or repeated epidural or spinal puncture.
Patients should be frequently monitored for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.
The physician should consider the potential benefit versus risk before neuraxial intervention, in patients anticoagulated or to be anticoagulated for thromboprophylaxis.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Subcutaneous:
Iprivask: 15 mg (1 ea [DSC])
Pharmacology
Mechanism of Action
Desirudin is a direct, highly selective thrombin inhibitor. Reversibly binds to the active thrombin site of free and clot-associated thrombin. Inhibits fibrin formation, activation of coagulation factors V, VII, and XIII, and thrombin-induced platelet aggregation resulting in a dose-dependent prolongation of the activated partial thromboplastin time (aPTT).
Pharmacokinetics/Pharmacodynamics
Absorption
Subcutaneous: Complete
Distribution
Vdss: 0.25 L/kg
Metabolism
Stepwise degradation from the C-terminus catalyzed by carboxypeptidase(s)
Excretion
Urine (40% to 50% as unchanged drug)
Time to Peak
Plasma: 1 to 3 hours
Half-Life Elimination
~2 hours; Prolonged with renal impairment (CrCl <31 mL/minute/1.73 m2: Up to 12 hours)
Use: Labeled Indications
Deep vein thrombosis, prophylaxis: Prophylaxis of deep vein thrombosis (DVT) in patients undergoing hip-replacement surgery
Contraindications
Hypersensitivity to natural or recombinant hirudins or any component of the formulation; active bleeding and/or irreversible coagulation disorders
Dosage and Administration
Dosing: Adult
Note: Iprivask has been discontinued in the US for more than 1 year.
Note: Initial dose may be given up to 5 to 15 minutes prior to surgery (after induction of regional anesthesia, if used); has been administered for up to 12 days (average: 9 to 12 days) in clinical trials
DVT prophylaxis: SubQ: 15 mg every 12 hours; interrupt therapy if aPTT exceeds 2 times control; resume at a reduced dose (based on the degree of aPTT abnormality) when aPTT is <2 times control
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Attach enclosed vial adapter to vial containing desirudin. Attach provided syringe containing diluent to adapter on vial. Slowly push plunger down to transfer entire contents of syringe into vial. Do not remove syringe from vial adapter. Gently swirl solution; powder will dissolve within 10 seconds. Resultant solution concentration is 31.5 mg/mL (15.75 mg/0.5 mL provides a 15 mg dose). Turn vial upside down; withdraw appropriate dose amount back into syringe. Remove syringe from vial. Attach enclosed Eclipse™ needle; pull pink lever down and uncap needle; ready for injection. After injection, flip up pink lever to cover needle until it snaps into place; dispose of syringe appropriately.
Administration
SubQ: Do not administer IM; for deep SubQ administration only. Administration should be alternated between the left and right anterolateral and left and right posterolateral thigh or abdominal wall. Insert whole needle length into a skin fold held between the thumb and forefinger; the skin fold should be held throughout the injection. Do not rub injection site.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Following reconstitution, solution may be stored at room temperature for up to 24 hours; protect from light. Discard unused solution after 24 hours.
Drug Interactions
Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Anticoagulants: May enhance the anticoagulant effect of Desirudin. Consider therapy modification
Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination
Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy
Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy
Corticosteroids (Systemic): May enhance the anticoagulant effect of Desirudin. More specifically, corticosteroids may increase hemorrhagic risk during desirudin treatment. Management: Discontinue treatment with systemic corticosteroids prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification
Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination
Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy
Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy
Dextran: May enhance the anticoagulant effect of Desirudin. More specifically, dextran may increase hemorrhagic risk during desirudin treatment. Management: Discontinue treatment with dextran prior to desirudin initiation when possible. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Avoid combination
Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Avoid combination
Estrogen Derivatives: May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Exceptions: Tibolone. Consider therapy modification
Fat Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Hemin: May enhance the anticoagulant effect of Anticoagulants. Avoid combination
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Management: Avoid such combinations when possible. If used concomitantly, increase diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds). Consider therapy modification
Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy
Inotersen: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Monitor therapy
MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Avoid combination
Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy
Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination
Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Oritavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Monitor therapy
Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Progestins: May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification
Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy
Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination
Salicylates: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Telavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Monitor therapy
Thrombolytic Agents: May enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with thrombolytic agents prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification
Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Urokinase: May enhance the anticoagulant effect of Anticoagulants. Avoid combination
Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Avoid combination
Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy
Adverse Reactions
As with all anticoagulants, bleeding is the major adverse effect. Hemorrhage may occur at any site.
2% to 10%:
Cardiovascular: Deep vein thrombophlebitis (2%)
Dermatologic: Wound secretion (4%)
Gastrointestinal: Nausea (2%)
Hematologic & oncologic: Hematoma (6%), anemia (3%), major hemorrhage (≤3%; may include hemophthalmos, intracranial hemorrhage, intraspinal hemorrhage, prosthetic joint hemorrhage, or retroperitoneal hemorrhage)
Local: Residual mass at injection site (4%)
<2%, postmarketing, and/or case reports: Anaphylactoid reaction, anaphylaxis, cerebrovascular disease, decreased hemoglobin, dizziness, epistaxis, fever, hematemesis, hematuria, hemorrhage (fatal), hypersensitivity reaction, hypotension, leg pain, lower extremity edema, thrombosis, vomiting, wound healing impairment
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylaxis/hypersensitivity reactions: Allergic and hypersensitivity reactions, including anaphylaxis and fatal anaphylactoid reactions have been reported with other hirudin derivatives. Exercise caution when re-exposing patients (anaphylaxis has been reported).
- Bleeding: Can occur at any site (eg, brain, GI tract, spleen, rectum, vagina); fatal and serious bleeding events have been reported. Certain patients are at increased risk of bleeding. Risk factors include recent major surgery; organ biopsy or puncture of a noncompressible vessel within the last month; intracranial or intraocular bleeding (including diabetic [hemorrhagic] retinopathy); recent ischemic stroke; history of gastrointestinal or pulmonary bleeding within the past 3 months; bacterial endocarditis; congenital or acquired bleeding disorders; severe uncontrolled hypertension; history of hemorrhagic stroke; thrombocytopenia or platelet defects; renal impairment; hepatic impairment; or in patients undergoing invasive procedures. Do not administer with other agents that increase the risk of hemorrhage unless coadministration cannot be avoided. Monitor patient closely for signs and/or symptoms of bleeding.
Disease-related concerns:
- Hepatic impairment: Use with caution; risk of bleeding may be increased.
- Renal impairment: Use with caution, especially in patients with moderate-to-severe renal impairment (CrCl <60 mL/minute/1.73 m2); dosage reduction is necessary; monitor aPTT and renal function daily.
Special populations:
- Elderly: Use with caution in the elderly; elimination half-life prolonged in patients >75 years of age.
Other warnings/precautions:
- Appropriate use: Do not administer intramuscularly (IM). Do not use interchangeably (unit-for-unit) with other hirudins.
- Neuraxial anesthesia: [U.S. Boxed Warning]: Patients with recent or anticipated neuraxial anesthesia (epidural or spinal anesthesia) or spinal puncture are at risk of developing an epidural or spinal hematoma resulting in long-term or permanent paralysis. Consider risk versus benefit prior to neuraxial anesthesia; risk is increased by the use of indwelling spinal catheters for administration of analgesia or concomitant agents which may alter hemostasis, as well as traumatic or repeated epidural or spinal puncture. Patient should be observed closely for bleeding and signs and symptoms of neurological impairment.
Monitoring Parameters
Signs and symptoms of bleeding; aPTT (daily in patients with increased risk of bleeding and/or renal impairment); serum creatinine (daily in patients with renal impairment).
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in animal reproduction studies. Data are insufficient to evaluate the safety of thrombin inhibitors during pregnancy (Guyatt, 2012).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), severe dizziness, passing out, a fall hitting head, signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), back pain, signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), or injection site redness or edema (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
