Desirudin warnings and precautions: Difference between revisions
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Revision as of 01:53, 3 February 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]
Warnings and Precautions
WARNINGS
Renal Insufficiency
Iprivask must be used with caution in patients with renal impairment, particularly in those with moderate and severe renal impairment (creatinine clearance ≤60 mL/min/1.73 m2 body surface area) (see CLINICAL PHARMACOLOGY, Special Populations, Renal Insufficiency). Dose reductions by factors of three and nine are recommended for patients with moderate and severe renal impairment respectively (see DOSAGE AND ADMINISTRATION). In addition, daily aPTT and serum creatinine monitoring are recommended for patients with moderate or severe renal impairment (see PRECAUTIONS, Laboratory Tests).
Hemorrhagic Events
Iprivask is not intended for intramuscular injection as local hematoma formation may result.
Iprivask, like other anticoagulants, should be used with caution in patients with increased risks of hemorrhage such as those with recent major surgery, organ biopsy or puncture of a non-compressible vessel within the last month; a history of hemorrhagic stroke, intracranial or intraocular bleeding including diabetic (hemorrhagic) retinopathy; recent ischemic stroke, severe uncontrolled hypertension, bacterial endocarditis, a known hemostatic disorder (congenital or acquired, e.g. hemophilia, liver disease) or a history of gastrointestinal or pulmonary bleeding within the past 3 months.
Bleeding can occur at any site during therapy with Iprivask. An unexplained fall in hematocrit or blood pressure should lead to a search for a bleeding site.
Spinal/Epidural Anesthesia
As with other anticoagulants, there is a risk of neuraxial hematoma formation with the concurrent use of desirudin and spinal/epidural anesthesia, which has the potential to result in long term or permanent paralysis. The risk may be greater with the use of post-operative indwelling catheters or the concomitant use of additional drugs affecting hemostasis such as NSAIDs (Non-Steroidal Anti-Inflammatory Drugs), platelet inhibitors or other anticoagulants (see Boxed WARNING and PRECAUTIONS, Drug Interactions). The risk may also be increased by traumatic or repeated neuraxial puncture.
To reduce the potential risk of bleeding associated with the concurrent use of desirudin and epidural or spinal anesthesia/analgesia, the pharmacokinetic profile of the drug should be considered (see CLINICAL PHARMACOLOGY, Pharmacokinetic properties) 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 (see DOSAGE and ADMINISTRATION).
Should the physician decide to administer anticoagulation in the context of epidural/spinal anesthesia, extreme vigilance and frequent monitoring must be exercised to detect any 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. Patients should be instructed to inform their physician immediately if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, 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 (see also WARNINGS, hemorrhage, and PRECAUTIONS, Drug Interactions).
Iprivask cannot be used interchangeably with other hirudins as they differ in manufacturing process and specific biological activity (ATUs). Each of these medicines has its own instructions for use.
PRECAUTIONS
Antibodies/Re-exposure
Antibodies have been reported in patients treated with hirudins. Potential for cross-sensitivity to hirudin products cannot be excluded. Irritative skin reactions were observed in 9/322 volunteers exposed to Iprivask by subcutaneous injection or IV bolus or infusion in single or multiple administrations of the drug. Allergic events were reported in <2% of patients who were administered desirudin in Phase III clinical trials. Allergic events were reported in 1% of patients receiving unfractionated heparin and 1% of patients receiving enoxaparin. Hirudin-specific IgE evaluations may not be indicative of sensitivity to Iprivask as this test was not always positive in the presence of symptoms. Very rarely, anti-hirudin antibodies have been detected upon re-exposure to desirudin. (See ADVERSE REACTIONS, Non-hemorrhagic Events, Allergic Reactions). Fatal anaphylactoid reactions have been reported during hirudin therapy.
Hepatic Insufficiency/Liver Injury
No information is available about the use of desirudin in patients with hepatic insufficiency/liver injury. Although Iprivask is not significantly metabolized by the liver, hepatic impairment or serious liver injury (e.g., liver cirrhosis) may alter the anticoagulant effect of Iprivask due to coagulation defects secondary to reduced generation of vitamin K-dependent coagulation factors. Iprivask should be used with caution in these patients.
Laboratory Tests
Activated partial thromboplastin time (aPTT) should be monitored daily in patients with increased risk of bleeding and/or renal impairment. Serum creatinine should be monitored daily in patients with renal impairment. Peak aPTT should not exceed two times control. Should peak aPTT exceed this level, dose reduction is advised based on the degree of aPTT abnormality (see DOSAGE and ADMINISTRATION, Initial Dosage, Use in Renal Insufficiency). If necessary, therapy with desirudin should be interrupted until aPTT falls to less than two times control, at which time treatment with desirudin can be resumed at a reduced dose. (See Drug Interactions for information on use of Iprivask in conjunction with other drugs affecting coagulation). Thrombin time (TT) is not a suitable test for routine monitoring of Iprivask therapy (seeCLINICAL PHARMACOLOGY, Mechanism of Action). Dose adjustments based on serum creatinine may be necessary (see DOSAGE AND ADMINISTRATION, Use in Renal Insufficiency).
Drug Interactions
Any agent which may enhance the risk of hemorrhage should be discontinued prior to initiation of desirudin therapy. These agents include medications such as Dextran 40, systemic glucocorticoids, thrombolytics, and anticoagulants. If co-administration cannot be avoided, close clinical and laboratory monitoring should be conducted. During prophylaxis of venous thromboembolism, concomitant treatment with heparins (unfractionated and low-molecular weight heparins) or dextrans is not recommended. The effects of desirudin and unfractionated heparins on prolongation of aPTT are additive.
As with other anticoagulants, desirudin should be used with caution in conjunction with drugs which affect platelet function. These medications include systemic salicylates, NSAIDS including ketorolac, acetylsalicylic acid, ticlopidine, dipyridamole, sulfinpyrazone, clopidogrel, abciximab and other glycoprotein IIb/IIIa antagonists (seePRECAUTIONS, Laboratory Tests).
Use in patients switching from oral anticoagulants to Iprivask or from Iprivask to oral anticoagulants. The concomitant administration of warfarin did not significantly affect the pharmacokinetic effects of desirudin. When warfarin and desirudin were co-administered, greater inhibition of hemostasis measured by activated partial thromboplastin time (aPTT), prothrombin time (PT), and international normalized ratio (INR) was observed. If a patient is switched from oral anticoagulants to Iprivask therapy or from Iprivask 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.[1]
References
- ↑ "IPRIVASK (DESIRUDIN) KIT [MARATHON PHARMACEUTICALS, LLC]". Retrieved 3 February 2014.