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Iprivask
Classes
Direct Thrombin Inhibitors
Administration
For storage information, see specific product information within the How Supplied section.
NOTE: Desirudin cannot be used interchangeably with other hirudins (e.g., bivalirudin, lepirudin) because differences exist in manufacturing process and specific biological activity (ATUs).
Visually inspect parenteral products for particulate matter and discoloration prior to administration. Do not use solutions that are cloudy or contain particles.
Desirudin is not approved by the FDA for intravenous administration.
Specific directions for intravenous reconstitution and administration are not available at this time.
Desirudin is administered by subcutaneous injection. Do not administer intramuscularly.
Do not mix desirudin injection with other injections, solvents, or parenteral fluids.
Reconstitution for subcutaneous (SC) injection:
Reconstitute each vial with 0.5 mL of provided diluent. Shake the vial gently until the drug is fully reconstituted. The injection should be a clear, colorless solution. Once reconstituted, each 0.5 mL contains 15.75 mg desirudin.
The reconstituted solution should be used immediately; however, it remains stable for up to 24 hours at room temperature and protected from light. Discard any unused solution appropriately.
Subcutaneous (SC) injection:
Patients should be sitting or lying down and desirudin administered by deep subcutaneous injection.
Using a syringe with a 26 or 27 gauge needle which is approximately 0.5-inch in length, withdraw the entire reconstituted solution into the syringe. Inject the total volume subcutaneously. Administration should be alternated between the left and right anterolateral and left and right posterolateral thigh or abdominal wall. The whole length of the needle should be introduced into a skin fold held between the thumb and forefinger; the skin fold should be held throughout the injection. To minimize bruising, do not rub the injection site after completion of the injection.
Adverse Reactions
retroperitoneal bleeding / Delayed / 0-1.0
hematemesis / Delayed / 0-1.0
intracranial bleeding / Delayed / 0-1.0
thrombosis / Delayed / 0-1.0
ocular hemorrhage / Delayed / 0-1.0
GI bleeding / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
spinal hematoma / Delayed / Incidence not known
bleeding / Early / 30.0-30.0
hematoma / Early / 6.0-6.0
anemia / Delayed / 3.0-3.0
phlebitis / Rapid / 2.0-2.0
hypotension / Rapid / 0-1.0
edema / Delayed / 0-1.0
hematuria / Delayed / 0-1.0
impaired wound healing / Delayed / 0-1.0
antibody formation / Delayed / 0-1.0
injection site reaction / Rapid / 4.0-4.0
fever / Early / 0-1.0
vomiting / Early / 0-1.0
dizziness / Early / 0-1.0
epistaxis / Delayed / 0-1.0
nausea / Early / 0-1.0
skin irritation / Early / 0-1.0
Boxed Warning
Concurrent use of desirudin or other anticoagulants with neuraxial anesthesia (epidural anesthesia, spinal anesthesia) or lumbar puncture increases the risk of developing an epidural or spinal hematoma. This can result in long-term or permanent paralysis. The risk is greater with the use of post-operative indwelling catheters or the concomitant use of additional drugs affecting hemostasis such as NSAIDs, platelet inhibitors, or other anticoagulants. The risk also appears to be increased by traumatic or repeated epidural or spinal puncture. To reduce the potential risk of bleeding associated with concurrent use of desirudin and neuraxial anesthesia, the pharmacokinetic profile of desirudin should be considered when scheduling or using epidural or spinal anesthesia in proximity to desirudin administration. The physician should consider placement of the catheter prior to initiating desirudin and removal of the catheter when the anticoagulant effect of desirudin is low. Patients should be frequently monitored for signs and symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), bowel and/or bladder dysfunction. If neurological compromise is noted, urgent diagnosis and treatment including spinal cord decompression should be initiated. The physician should consider the potential benefit versus risk before neuraxial intervention, in patients anticoagulated or to be anticoagulated for thromboprophylaxis.
Common Brand Names
Iprivask
Dea Class
Rx
Description
Parenteral recombinant analog of thrombin inhibitor hirudin; used for preventing DVT in patients undergoing elective hip replacement surgery; studied for acute coronary syndromes.
Dosage And Indications
The recommended initial dose is 15 mg subcutaneous every 12 hours with the first dose given 5 to 15 minutes prior to surgery but after induction of regional block anesthesia, if used. Up to 12 days of treatment (average duration 9 to 12 days) has been well-tolerated in clinical trials.
40 mg IV bolus then 0.2 mg/kg/hour continuous IV infusion for 24 hours, followed by 40 mg subcutaneously twice daily for 3 additional days. Desirudin was associated with significantly fewer early cardiac events (within 96 hours) than heparin; however, there was no long-term benefit over heparin in a single study.
0.1 mg/kg IV bolus followed by 0.1 mg/kg/hour continuous IV infusion. In the treatment of acute coronary syndromes (STEMI, NSTEMI, unstable angina), data from the GUSTO IIb and TIMI 9B trials show that desirudin was at least as effective as heparin when used as adjunctive therapy in patients treated with thrombolytic therapy and aspirin. Desirudin was administered for 72 to 120 hours (3 to 5 days) in the GUSTO IIb study and for 96 hours in the TIMI 9B study. Minor bleeding was more frequently associated with desirudin than heparin in these trials. The use of desirudin for the management of ACS is not discussed in clinical practice guidelines.
Dosage not established. Guidelines do not include desirudin. 20 to 40 mg IV once followed by 0.16 to 0.2 mg/kg/hour continuous IV infusion for 24 hours with or without subsequent 40 mg subcutaneously twice daily for 3 days has been used.
†Indicates off-label use
Dosing Considerations
Studies have not been performed in patients with hepatic impairment; specific dosage guidelines have not been established.
Renal ImpairmentCrCl > 60 mL/min: No dosage adjustment needed.
CrCl >= 31—60 mL/min: 5 mg subcutaneously every 12 hours. 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; resume therapy at a reduced dose guided by the initial degree of aPTT abnormality.
CrCl < 31 mL/min: 1.7 mg subcutaneously every 12 hours. 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; consider further dose reductions guided by the initial degree of aPTT abnormality.
Drug Interactions
Abciximab: (Major) The use of abciximab within 7 days of use an oral anticoagulant is contraindicated unless the patient's prothrombin time is less than or equal to 1.2 times the control value. Because abciximab inhibits platelet aggregation, additive effects may be seen when abciximab is given in combination with other agents that affect hemostasis such as other platelet inhibitors (e.g. aspirin, ASA, clopidogrel, dipyridamole, ticlopidine), thrombolytic agents (e.g. alteplase, reteplase, streptokinase), and anticoagulants (e.g., heparin, warfarin). However, in clinical trials with abciximab, aspirin and heparin were administered concomitantly. The bleeding risk is significantly increased with concurrent abciximab and thrombolytic therapy; the risks of combination therapy should be weighed against the potential benefits. The GUSTO V study evaluated reduced-dose reteplase in combination with full dose abciximab, in comparison to full dose reteplase alone in patients with acute myocardial infarction (MI); all patients received concurrent aspirin and heparin therapy. The combination regimen was associated with a two-fold increase in moderate to severe non-intracranial bleeding complications, including spontaneous GI bleeding. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Although NSAIDs lacks platelet inhibitory effects, an increased risk for GI bleeding is possible when NSAIDs are administered during abciximab therapy.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of anticoagulants with ado-trastuzumab emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding, with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving anticoagulation therapy, others had no known additional risk factors.
Altretamine: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Anagrelide: (Moderate) Although anagrelide inhibits platelet aggregation at high doses, there is a potential additive risk for bleeding if anagrelide is given in combination with other agents that effect hemostasis such as other anticoagulants. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. An in vivo interaction study in humans demonstrated that a single 1 mg dose of anagrelide administered concomitantly with a single dose of aspirin 900 mg was well tolerated; there was no effect on bleeding time, PT, or PTT. However, aspirin alone produced a marked inhibition of platelet aggregation ex vivo; anagrelide enhanced the platelet inhibition effects of aspirin slightly. Patients may be at increased risk of bleeding if anagrelide is administered with aspirin.
Antithrombin III: (Major) Any agent which may enhance the risk of hemorrhage (e.g., anticoagulants) should generally be discontinued before initiating desirudin therapy. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted. If a patient is switched from oral anticoagulants to desirudin therapy or from desirudin to oral anticoagulants, the anticoagulant activity should continue to be closely monitored with appropriate methods. That activity should be taken into account in the evaluation of the overall coagulation status of the patient during the switch.
Antithymocyte Globulin: (Moderate) Drugs that can cause thrombocytopenia, such as antithymocyte globulin, may lead to an increased risk of bleeding when given concurrently with anticoagulants.
Apixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if apixaban and other anticoagulants are used concomitantly. If switching from apixaban to another anticoagulant, discontinue apixaban and start the other anticoagulant at the usual time of the next dose of apixaban. If switching from another anticoagulant to apixaban, discontinue the other anticoagulant and start apixaban at the usual time of the next dose of the other anticoagulant. Coadministration of apixaban and other anticoagulants may increase the risk of bleeding.
Argatroban: (Major) Any agent which may enhance the risk of hemorrhage, including other anticoagulants, should generally be discontinued before initiating desirudin therapy. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted.
Arsenic Trioxide: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents and anticoagulants concomitantly.
Aspirin, ASA: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Carisoprodol: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Dipyridamole: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation. (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis.
Aspirin, ASA; Omeprazole: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Oxycodone: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Aspirin, ASA; Pravastatin: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Betrixaban: (Major) Avoid concurrent use of betrixaban with thrombin inhibitors due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and other anticoagulants are used concomitantly. Coadministration of betrixaban and other anticoagulants may increase the risk of bleeding.
Bismuth Subsalicylate: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Bivalirudin: (Major) Any agent which may enhance the risk of hemorrhage, including other anticoagulants, should generally be discontinued before initiating desirudin therapy. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted.
Caplacizumab: (Moderate) Assess and monitor closely for bleeding with concomitant use of caplacizumab and anticoagulants. Concomitant use of caplacizumab with any anticoagulant may increase the risk of bleeding. Interrupt caplacizumab use if clinically significant bleeding occurs.
Carbenicillin: (Moderate) Some penicillins (e.g., carbenicillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Chlorambucil: (Moderate) Due to the thrombocytopenic effects of chlorambucil, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Choline Salicylate; Magnesium Salicylate: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Cilostazol: (Moderate) The safety of cilostazol has not been established with concomitant administration of anticoagulants. Because cilostazol is a platelet aggregation inhibitor, concomitant administration with similar acting drugs could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution. Patients on anticoagulants should be monitored for changes in response to anticoagulation therapy if cilostazol is administered concurrently.
Citalopram: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Clofarabine: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Clopidogrel: (Moderate) Because clopidogrel inhibits platelet aggregation, a potential additive risk for bleeding exists if clopidogrel is given in combination with other agents that affect hemostasis such as anticoagulants.
Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking anticoagulants is advised. The efficacy and safety of administering injectable collagenase to a patient taking an anticoagulant within 7 days before the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection site.
Cytarabine, ARA-C: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Dabigatran: (Major) Any agent which may enhance the risk of hemorrhage should generally be discontinued before initiating desirudin therapy. These agents include anticoagulants. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted. If a patient is switched from oral anticoagulants to desirudin therapy or from desirudin to oral anticoagulants, the anticoagulant activity should continue to be closely monitored with appropriate methods. That activity should be taken into account in the evaluation of the overall coagulation status of the patient during the switch.
Dalteparin: (Moderate) Any agent which may enhance the risk of hemorrhage should generally be discontinued before initiating desirudin therapy, including anticoagulants. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted.
Danaparoid: (Major) Any agent which may enhance the risk of hemorrhage should generally be discontinued before initiating desirudin therapy, including anticoagulants. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted.
Danazol: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Dasatinib: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
Decitabine: (Moderate) Due to the thrombocytopenic effects of antineoplastic agents, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Decitabine; Cedazuridine: (Moderate) Due to the thrombocytopenic effects of antineoplastic agents, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Defibrotide: (Severe) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Denileukin Diftitox: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
Dextran: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis.
Drotrecogin Alfa: (Major) Treatment with drotrecogin alfa should be carefully considered in patients who are receiving or have received any anticoagulants. There is an additive risk of beeding.
Edoxaban: (Major) Avoid concurrent use of edoxaban with thrombin inhibitors due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if edoxaban and other anticoagulants are used concomitantly. Coadministration of edoxaban and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with edoxaban and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from edoxaban.
Eltrombopag: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Enoxaparin: (Moderate) Any agent which may enhance the risk of hemorrhage (e.g., enoxaparin) should generally be discontinued before initiating desirudin therapy. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted.
Epoprostenol: (Moderate) When used concurrently with anticoagulants, epoprostenol may increase the risk of bleeding.
Eptifibatide: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Escitalopram: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Esterified Estrogens; Methyltestosterone: (Moderate) Methyltestosterone can increase the effects of anticoagulants through reduction of procoagulant factor. Patients receiving oral anticoagulant therapy should be closely monitored, especially when methyltestosterone treatment is initiated or discontinued.
Estramustine: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Floxuridine: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
Fluorouracil, 5-FU: (Major) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents and anticoagulants concomitantly.
Fluoxetine: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Fluoxetine; Olanzapine: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Fluvoxamine: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Folate analogs: (Moderate) Due to the thrombocytopenic effects of folate analogs, when used as antineoplastic agents, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Fondaparinux: (Major) Discontinue thrombin inhibitors before starting fondaparinux due to the increased bleeding risk, unless these agents are essential. If coadministration is necessary, monitor patients closely and promptly evaluate any signs or symptoms of bleeding.
Garlic, Allium sativum: (Moderate) Garlic produces clinically significant antiplatelet effects so additive risk of bleeding may occur if anticoagulants are given in combination. Avoid concurrent use of herbs which interact with anticoagulants when possible. If garlic dietary supplements are taken, monitor the INR or other appropriate parameters to attain clinical and anticoagulant endpoints. In regard to warfarin, published data are limited to a random case report; however, the product labeling for warfarin includes garlic as having potential for interaction due to additive pharmacologic activity. A case of spontaneous spinal epidural hematoma, attributed to dysfunctional platelets from excessive garlic use in a patient not receiving concomitant anticoagulation, has been reported.
Ginger, Zingiber officinale: (Moderate) Additive bleeding may occur if anticoagulants are given in combination with ginger, zingiber officinale. Ginger inhibits thromboxane synthetase (platelet aggregation inducer) and is a prostacyclin agonist. Patients taking ginger and an anticoagulant should be monitored closely for bleeding.
Ginkgo, Ginkgo biloba: (Major) Ginkgo, Ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with Ginkgo biloba, with or without concomitant drug therapy. Since ginkgo produces clinically-significant antiplatelet effects, it should be used cautiously in patients drugs that inhibit platelet aggregation or pose a risk for bleeding, such as anticoagulants. Ginkgo, Ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with Ginkgo biloba, with or without concomitant drug therapy. Since ginkgo produces clinically-significant antiplatelet effects, it should be used cautiously in patients drugs that inhibit platelet aggregation or pose a risk for bleeding, such as anticoagulants (e.g., warfarin), aspirin, ASA or other platelet inhibitors, or thrombolytic agents. A patient who had been taking aspirin 325 mg/day PO for 3 years following coronary-artery bypass surgery, developed spontaneous bleeding into his eye after taking a standardized extract of Ginkgo biloba (Ginkoba commercial product) 40 mg PO twice daily for one week. The patient stopped taking the ginkgo but continued taking the aspirin with no recurrence of bleeding over a 3-month period. Other clinical data exist that describe spontaneous subdural hematomas associated with chronic ginkgo biloba ingestion.
Green Tea: (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. It is possible that the use of green tea may increase the risk of bleeding if co-administered with anticoagulants (e.g., enoxaparin, heparin, warfarin, and others) thrombolytic agents, or platelet inhibitors (e.g., aspirin, clopidogrel, cilostazol and others). Caution and careful monitoring of clinical and/or laboratory parameters are warranted if green tea is coadministered with any of these agents. Exogenous administration or occult sources of vitamin K may decrease or reverse the activity of warfarin; stability of the diet can be an important factor in maintaining anticoagulation goals. Occult sources of vitamin K include green tea and green tea dietary supplements. Published data are limited in regard to this interaction. A patient with previous INRs of 3.2. and 3.79 on a dose of 7.5mg daily of warfarin (goal INR 2.5 to 3.5) had an INR of 1.37. One month later, the patient's INR was 1.14. The patient admitted that he had started consuming 0.51 gallon of green tea daily approximately one week prior to the INR of 1.37. The patient denied noncompliance and other changes in diet, medications, or health. The patient discontinued green tea and one week later his INR was 2.55. While the amount of vitamin K in a single cup of brewed green tea may not be high (0.03 mcg/100 g), the actual amount may vary from cup to cup depending on the amount of tea leaves used, the length of time the tea bags are allowed to brew, and the volume of tea consumed. Additionally, if a patient drinks multiple cups of tea per day, the amount of vitamin K could reach significance. It is recommended that patients on warfarin maintain a stable intake of green tea.
Hemin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
Heparin: (Major) Any agent which may enhance the risk of hemorrhage should generally be discontinued before initiating desirudin therapy, including anticoagulants. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted. During prophylaxis of venous thromboembolism with desirudin, concomitant treatment with heparins [including unfractionated and low-molecular weight heparins (LMWHs)] or dextrans is not recommended. The effects of desirudin and unfractionated heparins on prolongation of aPTT are additive.
Hydroxyurea: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents and anticoagulants concomitantly.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with coagulation such as anticoagulants; the risk of bleeding may be increased. If coadministration with anticoagulants is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
Ibrutinib: (Moderate) The concomitant use of ibrutinib and anticoagulant agents such as desirudin may increase the risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were fatal. The mechanism for bleeding with ibrutinib therapy is not well understood.
Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Iloprost: (Moderate) When used concurrently with anticoagulants, inhaled iloprost may increase the risk of bleeding.
Imatinib: (Major) Due to the thrombocytopenic effects of imatinib an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. Monitor closely for bleeding.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and anticoagulants due to the potential risk of bleeding from thrombocytopenia. Consider discontinuation of anticoagulants in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
Interferon Alfa-2a: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
Interferon Alfa-2b: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
Interferon Alfa-2b; Ribavirin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
Interferon Alfacon-1: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
Interferon Alfa-n3: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
Intravenous Lipid Emulsions: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Lepirudin: (Major) Any agent which may enhance the risk of hemorrhage, including other anticoagulants, should generally be discontinued before initiating desirudin therapy. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted.
Lomustine, CCNU: (Moderate) Due to the bone marrow suppressive and thrombocytopenic effects of lomustine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Magnesium Salicylate: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Methoxsalen: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs such as increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM. Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians should consider using methylsulfonylmethane, MSM with caution in patients who are taking anticoagulants such as warfarin until data confirming the safety of MSM in patients taking these drugs are available. During one of the available, published clinical trials in patients with osteoarthritis, those patients with bleeding disorders or using anticoagulants or antiplatelets were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving warfarin should be observed for increased bleeding.
Methyltestosterone: (Moderate) Methyltestosterone can increase the effects of anticoagulants through reduction of procoagulant factor. Patients receiving oral anticoagulant therapy should be closely monitored, especially when methyltestosterone treatment is initiated or discontinued.
Mifepristone: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. Consider an alternative to mifepristone in these circumstances. When mifepristone is used for other condtions, such as Cushing's disease, an interaction with thrombin inhibitors is not expected; however, follow usual cautions and monitor as per standard of care.
Miltefosine: (Moderate) Caution is advised when administering miltefosine with anticoagulants, as use of these drugs together may increase risk for bleeding. Miltefosine, when administered for the treatment of visceral leishmaniasis, has been associated with thrombocytopenia; monitor platelet counts in patients receiving treatment for this indication. In addition, monitor closely for increased bleeding if use in combination with an anticoagulant.
Mycophenolate: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Nandrolone Decanoate: (Moderate) Androgens can enhance the effects of anticoagulants. Dosage of the anticoagulant may have to be decreased in order to maintain prothrombin time at the desired therapeutic level. When anabolic steroid or androgen therapy is started or stopped in patients on anticoagulant therapy, close monitoring is required. Additionally, nandrolone decanoate may generate a pharmacodynamic interaction with warfarin by independently affecting the activity of circulating coagulation proteins. Androgens reduce the amount or activity of circulating coagulant proteins thereby enhancing the anticoagulant effect of warfarin.
Natural Antineoplastics: (Moderate) Due to the risk of bleeding with natural antineoplastics, patients should receive other agents that may increase the risk of bleeding, such as anticoagulants.
Nelarabine: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Nintedanib: (Moderate) Nintedanib is a VEGFR inhibitor and may increase the risk of bleeding. Monitor patients who are taking anticoagulants closely and adjust anticoagulation therapy as necessary. Use nintedanib in patients with known risk of bleeding only if the anticipated benefit outweighs the potential risk.
Nonsteroidal antiinflammatory drugs: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use.
Obinutuzumab: (Moderate) Fatal hemorrhagic events have been reported in patients treated with obinutuzumab; all events occured during cycle 1. Monitor all patients for thrombocytopenia and bleeding, and consider withholding concomitant medications which may increase bleeding risk (i.e., anticoagulants, platelet inhibitors), especially during the first cycle.
Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and anticoagulants when the platelet count is less than 50,000 cells/microliter due to an increased risk of bleeding.
Oxandrolone: (Moderate) An increased effect of anticoagulants may occur with oxandrolone; the anticoagulant dosage may need adjustment downward with oxandrolone initiation or adjustment upward with oxandrolone discontinuation to maintain the desired clinical effect. Oxandrolone suppresses clotting factors II, V, VII, and X, which results in an increased prothrombin time. An increase in plasminogen-activator activity, and serum concentrations of plasminogen, protein C, and antithrombin III have occurred with several 17-alpha-alkylated androgens. For example, concurrent use of oxandrolone and warfarin may result in unexpectedly large increases in the INR or prothrombin time (PT). A multidose study of oxandrolone (5 or 10 mg PO twice daily) in 15 healthy individuals concurrently treated with warfarin resulted in significant increases in warfarin half-life and AUC; a 5.5-fold decrease in the mean warfarin dosage from 6.13 mg/day to 1.13 mg/day (approximately 80 to 85% dose reduction) was necessary to maintain a target INR of 1.5. According to the manufacturer, if oxandrolone therapy is initiated in a patient already receiving warfarin, the dose of warfarin may need to be decreased significantly to reduce the potential for excessive INR elevations and associated risk of serious bleeding events. The patient should be closely monitored with frequent evaluation of the INR and clinical parameter, and the dosage of warfarin should be adjusted as necessary until a stable target INR is achieved. Careful monitoring of the INR and necessary adjustment of the warfarin dosage are also recommended when the androgen therapy is changed or discontinued.
Paroxetine: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Pentosan: (Major) Pentosan is a weak anticoagulant. Pentosan has 1/15 the anticoagulant activity of heparin. Any agent which may enhance the risk of hemorrhage should generally be discontinued before initiating desirudin therapy. An additive risk of bleeding may be seen in patients receiving other anticoagulants in combination with pentosan. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted.
Phentermine; Topiramate: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation.
Piperacillin: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Piperacillin; Tazobactam: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Prasterone (DHEA) is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Prasterone (DHEA) is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Prasugrel: (Moderate) Concomitant use of prasugrel and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Rivaroxaban: (Major) Due to the increased bleeding risk, avoid concurrent use of rivaroxaban with thrombin inhibitors; the safety of concomitant use has not been studied. If a thrombin inhibitor is used during therapeutic transition periods, closely observe patients and promptly evaluate any signs or symptoms of blood loss.
Salicylates: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Salsalate: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation.
Selective serotonin reuptake inhibitors: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of serotonin norepinephrine reuptake inhibitors (SNRIs) and anticoagulants like desirudin. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Sertraline: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Sodium Iodide: (Moderate) Anticoagulants may alter sodium iodide I-131 pharmacokinetics and dynamics for up to 1 week after administrations.
Sulfinpyrazone: (Major) Sulfinpyrazone should be avoided when possible with concurrent anticoagulants, thrombin inhibitors, and thrombolytic agents due to potential for increased bleeding risk. Alternative uricosuric agents may be considered. Sulfinpyrazone is a platelet inhibitor and exhibits antithrombotic actions in addition to its uricosuric effects. Additive hematological effects are possible as a result of the platelet inhibitory effects of sulfinpyrazone; the sulfide metabolite of sulfinpyrazone appears responsible for this effect. Sulfinpyrazone is also known to markedly potentiate the effect of warfarin. Sulfinpyrazone may inhibit CYP2C9, leading to a decrease in the clearance of S-warfarin. If concurrent therapy is warranted, significant initial dosage reductions (e.g., 50%) of warfarin may be necessary, with further dosage adjusted based on INR values. The INR should be closely monitored during concurrent therapy with warfarin, particularly during the initiation or termination phases of sulfinpyrazone treatment.
Telavancin: (Moderate) Telavancin has no effect on coagulation or platelet aggregation; however, caution is advised when administering telavancin concurrently with anticoagulants as telavancin may interfere with laboratory tests used in monitoring these medications. The coagulation tests affected by telavancin include prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), activated clotting time, and coagulation based factor Xa tests. When measured shortly after completion of a telavancin infusion, the results of these tests are increased; however, the effects of telavancin on these tests dissipate over time as plasma concentrations of telavancin decrease. Therefore, when administering telavancin in conjunction with anticoagulants ensure that blood samples for these coagulation tests are collected as close as possible to the patient's next telavancin dose.
Thrombolytic Agents: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
Ticagrelor: (Moderate) Desirudin should be used with caution in conjunction with drugs which affect platelet function, due to the potential for an additive risk of bleeding.
Ticarcillin: (Moderate) Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Ticarcillin; Clavulanic Acid: (Moderate) Some penicillins (e.g., ticarcillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Ticlopidine: (Moderate) Because ticlopidine inhibits platelet aggregation, a potential additive risk for bleeding exists if ticlopidine is given in combination with other agents that affect hemostasis such as anticoagulants. Per the manufacturer of ticlopidine, if a patient is switched from an anticoagulant or a thrombolytic agent to ticlopidine, the former drug should be discontinued prior to the administration of ticlopidine.
Tinzaparin: (Moderate) Any agent which may enhance the risk of hemorrhage should generally be discontinued before initiating desirudin therapy. An additive risk of bleeding may be seen in patients receiving desiruden in combination with tinzaparin. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted.
Tipranavir: (Moderate) Caution should be used when administering tipranavir to patients receiving anticoagulants or platelet inhibitors. In clinical trials, there have been 14 reports of intracranial bleeding (intracranial hemorrhage, ICH), including 8 fatalities, in 13 out of 6,840 HIV infected patients receiving tipranavir as part of combination antiretroviral therapy. In many of these reports, the patients had other medical conditions (CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcoholism/alcohol abuse) or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events. The median time to onset of an ICH event was 525 days on tipranavir treatment. In general, there have been no reported patterns of abnormal coagulation parameters in patients receiving tipranavir, or preceding the development of ICH. Routine measurement of coagulation parameters does not appear to be indicated. An increased risk of ICH has previously been observed in patients with advanced HIV disease or AIDS; further investigations are ongoing to assess the role of tipranavir in ICH. While coadministration with warfarin does not result in altered warfarin concentrations, alterations
Tirofiban: (Moderate) Concomitant use of tirofiban and other agents that effect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Topiramate: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation.
Trazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with anticoagulants and to promptly report any bleeding events to the practitioner. Serotonergic agents may increase the risk of bleeding when combined with anticoagulants via inhibition of serotonin uptake by platelets; however, the absolute risk is not known. It would be prudent for clinicians to monitor the INR and patient's clinical status closely if trazodone is added to or removed from the regimen of a patient stabilized on anticoagulant therapy.
Treprostinil: (Moderate) When used concurrently with anticoagulants, treprostinil may increase the risk of bleeding.
Tretinoin, ATRA: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with anticoagulants is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease clotting could decrease the efficacy of verteporfin therapy.
Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with anticoagulants and to promptly report any bleeding events to the practitioner. Serotonergic agents may increase the risk of bleeding when combined with anticoagulants via inhibition of serotonin uptake by platelets; however, the absolute risk is not known. In addition, both vilazodone and warfarin are highly protein bound, which may result in displacement of warfarin from protein binding sites and an increased anticoagulant effect. It would be prudent for clinicians to monitor the INR and clinical status of the patient closely if vilazodone is added to or removed from the regimen of a patient stabilized on warfarin.
Vorapaxar: (Major) Avoid concomitant use of vorapaxar and warfarin or other anticoagulants. Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as anticoagulants.
Vorinostat: (Moderate) Concomitant use of vorinostat with anticoagulants may result in an additive risk of bleeding due to vorinostat-induced thrombocytopenia; monitor patients closely.
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving anticoagulants. Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with anticoagulants and to promptly report any bleeding events to the practitioner. Co-administration of vortioxetine and warfarin has not been shown to significantly affect the pharmacokinetics of either agent.
Warfarin: (Major) Any agent which may enhance the risk of hemorrhage should generally be discontinued before initiating desirudin therapy, including anticoagulants. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted. The concomitant administration of warfarin did not significantly affect the pharmacokinetic effects of desirudin; however, greater inhibition of hemostasis measured by aPTT, PT, and INR was observed with coadministration. If a patient is switched from oral anticoagulants to desirudin therapy or from desirudin to oral anticoagulants, the anticoagulant activity should continue to be closely monitored with appropriate methods. That activity should be taken into account in the evaluation of the overall coagulation status of the patient during the switch.
How Supplied
Iprivask Subcutaneous Inj Pwd F/Sol: 15mg
Maximum Dosage
>= 80 mg/day subcutaneously or > 0.1 mg/kg/hour IV is associated with unacceptable rates of bleeding for some indications.
>= 80 mg/day subcutaneously or > 0.1 mg/kg/hour IV is associated with unacceptable rates of bleeding for some indications.
Safety and efficacy have not been established.
ChildrenSafety and efficacy have not been established.
Mechanism Of Action
Desirudin is a selective thrombin inhibitor similar to bivalirudin and lepirudin, recombinant forms of the natural anticoagulant hirudin. One molecule of desirudin forms a tight stoichiometric complex with one molecule of thrombin and neutralizes its actions, including thrombin entrapped within established clots. It ultimately interferes with fibrin generation, platelet aggregation, factor XII activation, and other related biologic activities. Unlike heparin, desirudin inactivates thrombin without the need for antithrombin III. All thrombin-dependent coagulation assays are affected; aPTT values increase in a dose-dependent fashion. Thrombin times frequently exceed 200 seconds even at low desirudin plasma concentrations, thus, this test is not helpful in monitoring desirudin activity. Unlike heparin, recombinant hirudins such as desirudin are not inhibited by platelet factor IV. At therapeutic serum concentrations, desirudin has no effect on other enzymes of the hemostatic system such as factors IXa, Xa, kallikrein, plasmin, tissue plasminogen activator, or activated protein C. Additionally, it does not display any effect on other serine proteases, such as the digestive enzymes trypsin, chymotrypsin, or on complement activation by the classical or alternative pathways. No antagonists to direct thrombin inhibitors are known.
Pharmacokinetics
Desirudin is administered subcutaneously (SC). In the systemic circulation, desirudin binds specifically and directly to thrombin, forming an extremely tight, non-covalent complex with an inhibition constant of about 2.6 x 10-13 M; free or protein bound desirudin immediately binds circulating thrombin. The pharmacological effects of desirudin are not modified by co-administration with highly protein bound drugs (> 99%).
Human and animal data suggest that desirudin is primarily metabolized and eliminated by the kidney. It appears that desirudin is metabolized by stepwise degradation from the C-terminus possibly catalyzed by carboxypeptidase(s) such as carboxypeptidase A, originating from the pancreas. A minor portion of recovered drug in the urine (< 7%) is present as metabolites lacking one or two C-terminal amino acids. There is no evidence for the presence of other metabolites. It is not known if desirudin metabolites are pharmacologically active. Approximately 40—50% of an administered dose is excreted as unchanged drug in the urine.
Pharmacokinetic studies of intravenous (IV) desirudin show that desirudin is distributed into the extracellular space and that its volume of distribution is independent of the dose. Total clearance of desirudin is approximately 1.5 to 2.7 mL/min/kg after IV administration and is independent of dose. This clearance value is similar to the glomerular filtration rate (GFR). After IV administration, the elimination of desirudin from plasma is rapid with about 90% of the dose disappearing from plasma within 2 hours of the injection. Thereafter, desirudin plasma concentrations decline with a mean terminal elimination half-life (T½) of 2—3 hours.
Following administration of single doses of 0.1 to 0.75 mg/kg subcutaneously, desirudin is completely absorbed with peak plasma concentrations (Cmax) occurring within 1—3 hours after dosage administration. Both Cmax and area-under-the-curve (AUC) are dose proportional. Total clearance of desirudin is approximately 1.5 to 2.7 mL/min/kg after subcutaneous administration and is independent of dose. This clearance value is similar to the glomerular filtration rate (GFR). The mean terminal elimination half-life of desirudin is about 2 hours after subcutaneous administration.
Pregnancy And Lactation
According tot he manufacturer, it is not known whether desirudin is excreted in human milk. Due to its large molecular weight (approximately 7000 Daltons) and relatively short half-life (2—3 hours), excretion into breast milk is unlikely. Furthermore, because desirudin is a protein, any drug excreted would most likely be digested in the gut of the nursing infant. Although desirudin is not specifically addressed in the guidelines, the American College of Chest Physicians (ACCP) states that r-hirudin, a similar medication, may be continued while breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.