Desirudin

Desirudin
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi

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Black Box Warning

WARNING See full prescribing information for complete Boxed Warning. SPINAL/EPIDURAL HEMATOMAS: 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 Iprivask 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 non- steroidal 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.

Overview

Desirudin is a direct thrombin inhibitor that is FDA approved for the {{{indicationType}}} of deep vein thrombosis in patients undergoing elective hip replacement surgery. There is a Black Box Warning for this drug as shown here. Common adverse reactions include hemorrhage, injection site mass, wound secretion, anemia, deep thrombophlebitis, and nausea.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Prophylaxis of Deep Vein Thrombosis

• Dosing Information

• All patients should be evaluated for bleeding disorder risk before prophylactic administration of Iprivask.

• Initial Dosage

• In patients undergoing hip replacement surgery, the recommended dose of Iprivask is 15 mg every 12 hours administered by subcutaneous injection with the initial dose given up to 5 to 15 minutes prior to surgery, but after induction of regional block anesthesia, if used. Up to 12 days administration (average duration 9 to 12 days) of Iprivask has been well tolerated in controlled clinical trials.

• Dose in Renal Impairment

This image is provided by the National Library of Medicine.

• Dose in Hepatic Impairment

• In the absence of clinical studies in this population, dosing recommendations cannot be made at this time.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Desirudin in adult patients.

Non–Guideline-Supported Use

Prophylaxis of Coronary Thrombolysis in Acute Coronary Syndrome

• Equivalent or slightly better efficacy compared to heparin for thrombolysis in patients with acute coronary syndrome; desirudin administration is also associated with a lower early reinfarction rate.

Percutaneous Transluminal Coronary Angioplasty

• Intravenous desirudin (20 mgbolus followed by an infusion of 0.16 mg/kg/hr for 24 hours) is associated with a reduced early cardiac events in patients undergoing percutaneous transluminal coronary angioplasty.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

• Safety and effectiveness in pediatric patients have not been established.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Desirudin in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Desirudin in pediatric patients.

Contraindications

• Iprivask is contraindicated in patients with known hypersensitivity to natural or recombinant hirudins, and in patients with active bleeding and/or irreversible coagulation disorders.

Warnings

WARNING See full prescribing information for complete Boxed Warning. SPINAL/EPIDURAL HEMATOMAS: 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 Iprivask 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 non- steroidal 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.

• 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. 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 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.

• 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.

• 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.

• Renal Impairment

• 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). Dose reductions by factors of three and nine are recommended for patients with moderate and severe renal impairment respectively. In addition, daily aPTT and serum creatinine monitoring are recommended for patients with moderate or severe renal impairment.

• 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 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.

• 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. Fatal anaphylactoid reactions have been reported during hirudin therapy.

• Hepatic Impairment/Liver Injury

• No information is available about the use of desirudin in patients with hepatic impairment/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. 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. Thrombin time (TT) is not a suitable test for routine monitoring of Iprivask therapy. Dose adjustments based on serum creatinine may be necessary.

Adverse Reactions

Clinical Trials Experience

• In the Phase II and III clinical studies, desirudin was administered to 2159 patients undergoing elective hip replacement surgery to determine the safety and efficacy of Iprivask in preventing VTE in this population. Below is the safety profile of the Iprivask 15 mg (q12h) regimen from these 5 multicenter clinical trials.

• Hemorrhagic Events: The following rates of hemorrhagic events have been reported during clinical trials.

This image is provided by the National Library of Medicine.

• a – Includes hematomas which occurred at an incidence of 6% in the Iprivask and enoxaparin treatment groups and 5% in the heparin treatment group.
• b – Bleeding complications were considered serious if preoperative transfusion requirements exceeded 5 units of whole blood or packed red cells, or if total transfusion requirements up to postoperative Day 6 inclusive exceeded 7 units of whole blood or packed red cells, or total blood loss up to postoperative Day 6 inclusive exceeded 3500 mL.
• c – Bleeding complications were considered major if the hemorrhage was: (1) overt and it produced a fall in hemoglobin of ≥2g/dL or if it lead to a transfusion of 2 or more units of whole or packed cells outside the perioperative period (the time from start of surgery until up to 12 hours after); (2) Retroperitoneal, intracranial, intraocular, intraspinal, or occurred in a major prosthetic joint.

• Non-hemorrhagic Events

• Non-hemorrhagic adverse events occurring at ≥2% incidence in patients treated with Iprivask 15 mg (q 12h) during elective hip replacement surgery and considered to be remotely, possibly, or probably related to desirudin are provided below.

This image is provided by the National Library of Medicine.

• a – Represents events reported while on treatment, excluding unrelated adverse events
• b – All hemorrhages that occurred are included in Hemorrhagic Events.

• Related Adverse Events with a Frequency of <2% and >0.2% (in decreasing order of frequency): thrombosis, hypotension, leg edema, fever, decreased hemoglobin, hematuria, dizziness, epistaxis, vomiting, impaired healing, cerebrovascular disorder, leg pain, hematemesis.

• Allergic Reactions

• In clinical studies, allergic events were reported <2% overall and in 2% of patients who were administered 15 mg desirudin.

Postmarketing Experience

• In addition to adverse events reported from clinical trials the following adverse events have been identified during post approval use of Iprivask. These events were reported voluntarily from a population of unknown size and the frequency of occurrence cannot be determined precisely: rare reports of major hemorrhages, some of which were fatal, and anaphylactic/anaphylactoid reactions.

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 [see WARNINGS AND PRECAUTIONS, Laboratory Tests (5.6)].

• 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.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

xx
Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Desirudin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Desirudin during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Desirudin with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Desirudin with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Desirudin with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Desirudin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Desirudin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Desirudin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Desirudin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Desirudin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Desirudin in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Desirudin in the drug label.

Condition1

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Desirudin in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Desirudin in the drug label.

Pharmacology

There is limited information regarding Desirudin Pharmacology in the drug label.

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Desirudin in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Desirudin in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Desirudin in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Desirudin in the drug label.

Condition1

• Description

How Supplied

Storage

There is limited information regarding Desirudin Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Desirudin in the drug label.

Precautions with Alcohol

• Alcohol-Desirudin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• Iprivask®

Look-Alike Drug Names

• N/A

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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