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| __NOTOC__
| | #REDIRECT [[Argatroban#How Supplied]] |
| {{Argatroban}}
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| {{CMG}}; {{AE}} {{JH}}
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| ==Dosage forms and Stregths==
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| Each 50 mL glass vial contains 50 mg argatroban (1 mg/mL); and, as supplied, is ready for intravenous infusion. Dilution is not required.
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| Argatroban Injection is a clear, colorless to pale yellow solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if solution is cloudy, contains precipitates, or if the white flip top cap is not intact.
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| Vial may be inverted for use with a medical infusion set.
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| ====2.1 Dosing in Patients with Heparin-Induced Thrombocytopenia====
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| Initial Dosage:
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| Before administering argatroban, discontinue heparin therapy and obtain a baseline [[aPTT]]. The recommended initial dose of Argatroban for adult patients without hepatic impairment is 2 mcg/kg/min, administered as a continuous infusion (see Table 1).
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| {|
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| | [[File:Argatroban_01.png|thumb|800px]]
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| ''Monitoring Therapy:''
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| For use in HIT, therapy with Argatroban Injection is monitored using the aPTT with a target range of 1.5 to 3 times the initial baseline value (not to exceed 100 seconds). Tests of anticoagulant effects (including the aPTT) typically attain steady-state levels within 1 to 3 hours following initiation of Argatroban Injection. Check the [[aPTT]] 2 hours after initiation of therapy and after any dose change to confirm that the patient has attained the desired therapeutic range.
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| ''Dosage Adjustment:''
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| After the initiation of Argatroban Injection, adjust the dose (not to exceed 10 mcg/kg/min) as necessary to obtain a steady state [[aPTT]] in the target range [see Clinical Studies (14.1)].
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| ====2.2 Dosing in Patients Undergoing Percutaneous Coronary Intervention====
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| ''Initial Dosage:''
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| Initiate an infusion of Argatroban Injection at 25 mcg/kg/min and administer a bolus of 350 mcg/kg via a large bore intravenous line over 3 to 5 minutes (see Table 2). Check an activated [[clotting time]] (ACT) 5 to 10 minutes after the bolus dose is completed. The [[PCI]] procedure may proceed if the ACT is greater than 300 seconds.
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| ''Dosage Adjustment:''
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| If the [[ACT]] is less than 300 seconds, an additional intravenous bolus dose of 150 mcg/kg should be administered, the infusion dose increased to 30 mcg/kg/min, and the ACT checked 5 to 10 minutes later (see Table 2).
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| If the [[ACT]] is greater than 450 seconds, the infusion rate should be decreased to 15 mcg/kg/min, and the [[ACT]] checked 5 to 10 minutes later (Table 3).
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| Continue titrating the dose until a therapeutic [[ACT]] (between 300 and 450 seconds) has been achieved; continue the same infusion rate for the duration of the PCI procedure.
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| In case of dissection, impending abrupt closure, thrombus formation during the procedure, or inability to achieve or maintain an ACT over 300 seconds, additional bolus doses of 150 mcg/kg may be administered and the infusion dose increased to 40 mcg/kg/min. Check the ACT after each additional bolus or change in the rate of infusion.
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| {|
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| | [[File:Argatroban_02.png|thumb|800px]]
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| {|
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| | [[File:Argatroban_03.png|thumb|800px]]
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| ''Monitoring therapy:''
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| For use in PCI, therapy with Argatroban Injection is monitored using ACT. Obtain ACTs before dosing, 5 to 10 minutes after bolus dosing, following adjustments in the infusion rate, and at the end of the [[PCI]] procedure. Obtain additional ACTs every 20 to 30 minutes during a prolonged procedure.
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| ''Continued Anticoagulation after PCI:''
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| If a patient requires anticoagulation after the procedure, Argatroban Injection may be continued, but at a rate of 2 mcg/kg/min and adjusted as needed to maintain the [[aPTT]] in the desired range [see Dosage and Administration (2.1)].
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| ====2.3 Dosing in Patients with Hepatic Impairment====
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| For adult patients with HIT and moderate or severe hepatic impairment (based on Child-Pugh classification), an initial dose of 0.5 mcg/kg/min is recommended, based on the approximately 4-fold decrease in argatroban clearance relative to those with normal hepatic function. Monitor the aPTT closely, and adjust the dosage as clinically indicated.
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| ''Monitoring Therapy:''
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| Achievement of steady state aPTT levels may take longer and require more dose adjustments in patients with hepatic impairment compared to patients with normal hepatic function.
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| For patients with hepatic impairment undergoing PCI who have HIT or are at risk for HIT, carefully titrate argatroban until the desired level of anticoagulation is achieved. Use of Argatroban in [[PCI]] patients with clinically significant hepatic disease or AST/ALT levels ≥ 3 times the upper limit of normal should be avoided. [see Warnings and Precautions (5.2)].
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| ====2.4 Dosing in Pediatric Patients With Heparin-Induced Thrombocytopenia/Heparin-Induced Thrombocytopenia and Thrombosis Syndrome====
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| ''Initial Dosage:''
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| Initial argatroban infusion doses are lower for seriously ill pediatric patients compared to adults with normal hepatic function [see Use in Specific Populations (8.4)].
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| ''Monitoring Therapy:''
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| In general, therapy with argatroban is monitored using the aPTT. Tests of anticoagulant effects (including the [[aPTT]]) typically attain steady-state levels within one to three hours following initiation of argatroban in patients without hepatic impairment [see Warnings and Precautions (5.2)]. Dose adjustment may be required to attain the target [[aPTT]]. Check the [[aPTT]] two hours after initiation of therapy and after any dose change to confirm that the patient has attained the desired therapeutic range.
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| Dosage Adjustment: [see Use in Specific Populations (8.4)]
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| ====2.5 Conversion to Oral Anticoagulant Therapy====
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| ''Initiating Oral Anticoagulant Therapy''
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| When converting patients from Argatroban to oral anticoagulant therapy, consider the potential for combined effects on the International [[Normalized Ratio]] ([[INR]]). To avoid prothrombotic effects and to ensure continuous anticoagulation when initiating [[warfarin]], overlap Argatroban Injection and [[warfarin]] therapy. There are insufficient data available to recommend the duration of the overlap. Initiate therapy using the expected daily dose of [[warfarin]]. A loading dose of [[warfarin]] should not be used.
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| The relationship between [[INR]] and bleeding risk is altered when argatroban and [[warfarin]] are co-administered. The combination of argatroban and [[warfarin]] does not cause further reduction in the vitamin-K dependent factor Xa activity than that which is seen with [[warfarin]] alone. The relationship between [[INR]] obtained on combined therapy and [[INR]] obtained on [[warfarin]] alone is dependent on both the dose of argatroban and the thromboplastin reagent used. The [[INR]] value on [[warfarin]] alone ([[INR]]w) can be calculated from the [[INR]] value on combination argatroban and [[warfarin]] therapy [see Drug Interactions (7.2) and Clinical Pharmacology (12.2)].
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| ''Co-Administration of [[warfarin]] and Argatroban Injection at Doses up to 2 mcg/kg/min:''
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| Measure [[INR]] daily while Argatroban Injection and [[warfarin]] are co-administered. In general, with doses of Argatroban Injection up to 2 mcg/kg/min, Argatroban Injection can be discontinued when the [[INR]] is greater than 4 on combined therapy. After Argatroban Injection is discontinued, repeat the [[INR]] measurement in 4 to 6 hours. If the repeat [[INR]] is below the desired therapeutic range, resume the infusion of Argatroban Injection and repeat the procedure daily until the desired therapeutic range on [[warfarin]] alone is reached.
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| ''Co-Administration of [[warfarin]] and Argatroban Injection at Doses Greater than 2 mcg/kg/min:''
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| For doses greater than 2 mcg/kg/min, the relationship of [[INR]] between [[warfarin]] alone to the [[INR]] on [[warfarin]] plus argatroban is less predictable. In this case, in order to predict the [[INR]] on [[warfarin]] alone, temporarily reduce the dose of Argatroban Injection to a dose of 2 mcg/kg/min. Repeat the [[INR]] on Argatroban Injection and [[warfarin]] 4 to 6 hours after reduction of the Argatroban Injection dose and follow the process outlined above for administering Argatroban Injection at doses up to 2 mcg/kg/min.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = ARGATROBAN INJECTION, SOLUTION [GLAXOSMITHKLINE LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9c9616c0-a299-4fd5-c8ae-79e6db453595 | publisher = | date = | accessdate = }}</ref>
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| ==Reference==
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| {{reflist}}
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| {{FDA}}
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Hematology]]
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| [[Category:Drugs]]
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