Lepirudin (Refludan ®)
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Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]
| [100 mg] [250 ml] [As directed]
(Concentration: 0.4 mg/ml)
[100 mg] [500 ml] [Titrate]
Stability / Miscellaneous
| EXP: 1 DAY (RT).
Recombinant hirudin derived from yeast cells. Used for treatment of disseminated intravascular coagulation, in particular heparin-induced thrombocytopenia type II.
Mechanism of action: reacts with thrombin in a 1:1 molar ratio to form a noncovalent complex; directly inhibits all actions of thrombin. There is no physiologic inhibitor of lepirudin.
Lepirudin provides more stable level of anticoagulation than heparin. Lepirudin does not require endogenous cofactors and acts independently of antithrombin-III.
Preparation: Bolus dose: use concentration of 5 mg/ml. Dilute 50mg vial with 1 ml NS or sterile water, then transfer to at least 10 ml syringe and qs to 10ml with sterile water, NS or D5W.
DOSAGE AND ADMINISTRATION
* 0.4 mg/kg body weight (up to 110 kg) slowly intravenously (eg, over 15 to 20 seconds) as a bolus dose. CAUTION: Preparation of a Refludan bolus injection requires dilution following reconstitution in order to obtain the final concentration of 5 mg/mL.
Normally the initial dosage depends on the patient’s body weight. This is valid up to a body weight of 110 kg. In patients with a body weight exceeding 110 kg, the initial dosage should not be increased beyond the 110 kg body weight dose (maximal initial bolus dose of 44 mg, maximal initial infusion dose of 16.5 mg/h; see also DOSAGE AND ADMINISTRATION: Administration; Initial Intravenous Bolus, Table 7 and DOSAGE AND ADMINISTRATION: Administration; Intravenous Infusion, Table 8).
In general, therapy with REFLUDAN is monitored using the aPTT ratio (patient aPTT at a given time over an aPTT reference value, usually median of the laboratory normal range for aPTT, see DOSAGE AND ADMINISTRATION: Monitoring and Adjusting Therapy; Standard Recommendations). A patient baseline aPTT should be determined prior to initiation of therapy with REFLUDAN, since REFLUDAN should not be started in patients presenting with a baseline aPTT ratio of 2.5 or more, in order to avoid initial overdosing.
Monitoring and Adjusting Therapy
Use in Renal Impairment
Therefore, these recommendations are only tentative and aPTT monitoring should be used along with monitoring of renal status.
Dose adjustments should be based on creatinine clearance values, whenever available, as obtained from a reliable method (24 h urine sampling). If creatinine clearance is not available, the dose adjustments should be based on the serum creatinine.
In all patients with renal insufficiency, the bolus dose is to be reduced to 0.2 mg/kg body weight. CAUTION: Preparation of a Refludan bolus injection requires dilution following reconstitution in order to obtain the final concentration of 5 mg/mL.
The standard initial infusion rate given in DOSAGE AND ADMINISTRATION: Initial Dosage and DOSAGE AND ADMINISTRATION: Administration; Intravenous Infusion, Table 8 must be reduced according to the recommendations given in Table 6. Additional aPTT monitoring is highly recommended.
Table 6: Reduction of infusion rate in patients with renal impairment
Concomitant Use With Thrombolytic Therapy
* Initial intravenous bolus: 0.2 mg/kg body weight. CAUTION: Preparation of a Refludan bolus injection requires dilution following reconstitution in order to obtain the final concentration of 5 mg/mL
The number of patients receiving combined therapy was too small to identify differences in clinical outcome of patients who were started on both REFLUDAN and thrombolytic therapy as compared to those who were started on REFLUDAN alone. The combined incidences of death, limb amputation, or new TEC were 22.2% and 20.7%, respectively. While there was a 47% relative increase in the overall bleeding rate in patients who were started on both REFLUDAN and thrombolytic therapy (55.6% vs. 37.9%), there were no differences in the rates of serious bleeding events (fatal or life-threatening bleeds, bleeds that were permanently or significantly disabling, overt bleeds requiring transfusion of 2 or more units of packed red blood cells, bleeds necessitating surgical intervention, intracranial bleeds) between the groups (11.1% vs. 11.2%). Although no intracranial bleeding has been observed in any of these patients, there have been reports of intracranial bleeding in the presence or absence of concomitant thrombolytic therapy. (See package insert for WARNINGS and ADVERSE REACTIONS.)
Special attention should be paid to the fact that thrombolytic agents per se may increase the aPTT ratio. Therefore, aPTT ratios with a given plasma level of lepirudin are usually higher in patients who receive concomitant thrombolysis than in those who do not.
Use in Patients Scheduled for a Switch to Oral Anticoagulation
In REFLUDAN-treated patients receiving overlapping therapy with oral anticoagulants, there may be a small reduction in INR upon cessation of REFLUDAN treatment. When transitioning from REFLUDAN to oral anticoagulation, PT/INR should be monitored closely until results stabilize in the therapeutic range.
If a patient is scheduled to receive coumarin derivatives (vitamin K antagonists) for oral anticoagulation after REFLUDAN therapy, the dose of REFLUDAN should first be gradually reduced in order to reach an aPTT ratio just above 1.5 before initiating oral anticoagulation. Coumarin derivatives should be initiated only when platelet counts are normalizing. The intended maintenance dose should be started with no loading dose. To avoid prothrombotic effects when initiating coumarin, continue parenteral anticoagulation for 4 to 5 days (see oral anticoagulant package insert for information.) The parenteral agent can be discontinued when the INR stabilizes within the desired target range.
Use REFLUDAN before the expiration date given on the carton and container.
Reconstitution and further dilution are to be carried out under sterile conditions:
* For reconstitution, Sterile Water for Injection USP or 0.9% Sodium Chloride Injection USP are to be used.
Initial Intravenous Bolus
For intravenous bolus injection, use a solution with a concentration of 5 mg/mL.
Preparation of a REFLUDAN solution with a concentration of 5 mg/mL:
Table 7: Standard bolus injection volumes according to body weight for a 5 mg/mL concentration
*Dosage recommended for all patients with renal insufficiency (see DOSAGE AND ADMINISTRATION: Monitoring and Adjusting Therapy; Use in Renal Impairment).
Preparation of a REFLUDAN solution with a concentration of 0.2 or 0.4 mg/mL:
* Reconstitute two vials (each containing 50 mg of lepirudin) with 1 mL each using either Sterile Water for Injection USP or 0.9% Sodium Chloride Injection USP.
The infusion rate [mL/h] is to be set according to body weight (see Table 8 below and DOSAGE AND ADMINISTRATION: Initial Dosage).
Prescribing Information as of December 2006
Source: [package insert]
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user’s use of or reliance upon this material.PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. Read the disclaimer