Heparin-induced thrombocytopenia:
Continuous IV infusion:
Initial dose: 2 mcg/kg/minute; titrate to maintain aPTT in desired range. Note: Dose adjustment is necessary for critically ill patients and/or patients with hepatic impairment.
Critically ill patients : Initial dose: 1 mcg/kg/minute; usual dosing range: 0.25 to 1.5 mcg/kg/minute may be appropriate depending on the level of organ dysfunction (ACCP [Linkins 2012]; Beiderlinden 2007; Kiser 2005; Kiser 2011; Tardy-Poncet 2015).
Note: Usual dosage range for patients with moderate to severe hepatic impairment or heart failure: 0.25 to 0.5 mcg/kg/minute (ACCP [Linkins 2012]; Beiderlinden 2007; Kiser 2005; Kiser 2011; Tardy-Poncet 2015; Yarbrough 2012).
Maintenance dose: Measure aPTT after 2 hours. In critically ill patients, consider measuring aPTT 2 hours after initiation, then every 4 hours to allow for steady state to be achieved. Adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value, not exceeding 100 seconds; dosage should not exceed 10 mcg/kg/minute (Kiser 2011; Tardy-Poncet 2015).
Conversion to oral anticoagulant:
Note: Also consider referring to institutional protocols; optimal approach for conversion to oral therapy has not been established.
Conversion to warfarin: Because there may be a combined effect on the INR when argatroban is used concomitantly with warfarin, loading doses of warfarin should not be used. Initiate warfarin therapy at the expected daily dose. Optimal conversion strategy has not been identified if INR is already >4 on argatroban alone (eg, before starting warfarin); refer to institutional protocols.
Patients receiving ≤2 mcg/kg/minute of argatroban: Argatroban therapy can be stopped when the INR is >4 on combined warfarin and argatroban therapy; repeat INR measurement in 4 to 6 hours; if INR is below therapeutic level, argatroban therapy may be restarted. Repeat procedure daily until desired INR on warfarin alone is obtained.
Patients receiving >2 mcg/kg/minute of argatroban: Reduce dose of argatroban to 2 mcg/kg/minute; measure INR for argatroban and warfarin 4 to 6 hours after dose reduction; argatroban therapy can be stopped when the INR on warfarin and argatroban combined therapy is >4. Repeat INR measurement in 4 to 6 hours; if INR is below therapeutic level, argatroban therapy may be restarted. Repeat procedure daily until desired INR on warfarin alone is obtained.
Note: The American College of Chest Physicians suggests monitoring chromogenic factor X assay when transitioning from argatroban to warfarin (Garcia 2012) or overlapping administration of warfarin for a minimum of 5 days until INR is within target range; recheck INR after anticoagulant effect of argatroban has dissipated (Guyatt 2012). Factor X levels <45% have been associated with INR values >2 after the effects of argatroban have been eliminated (Arpino 2005).
Conversion to a direct-acting oral anticoagulant: Start direct-acting oral anticoagulant when argatroban infusion is stopped (consult institutional protocol if the aPTT is above the target range) (Dager 2018).
Percutaneous coronary intervention: IV:
Initial: Begin infusion of 25 mcg/kg/minute and administer bolus dose of 350 mcg/kg (over 3 to 5 minutes). ACT should be checked 5 to 10 minutes after bolus infusion; proceed with procedure if ACT >300 seconds.
Following initial bolus:
ACT <300 seconds: Give an additional 150 mcg/kg bolus, and increase infusion rate to 30 mcg/kg/minute (recheck ACT in 5 to 10 minutes).
ACT >450 seconds: Decrease infusion rate to 15 mcg/kg/minute (recheck ACT in 5 to 10 minutes).
Once a therapeutic ACT (300 to 450 seconds) is achieved, infusion should be continued for the duration of the procedure.
If dissection, impending abrupt closure, thrombus formation during PCI, or inability to achieve ACT >300 seconds: An additional bolus of 150 mcg/kg, followed by an increase in infusion rate to 40 mcg/kg/minute may be administered (recheck ACT after each additional bolus or change in infusion rate).
Note: Post-PCI anticoagulation, if required, may be achieved by continuing infusion at a reduced dose of 2 mcg/kg/minute, with close monitoring of aPTT; adjust infusion rate as needed. Recheck ACT after each additional bolus or change in infusion rate.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to severe impairment: No dosage adjustment necessary.
Dialysis: Dialyzable, ~20% removed over 4 hours during hemodialysis (NCS/SCCM [Frontera 2016]); removal during hemodialysis and continuous venovenous hemofiltration did not alter clinical efficacy when used for anticoagulation in renal replacement therapy (Tang 2005)
Heparin-induced thrombocytopenia:
Mild impairment (Child-Pugh class A): There are no specific dosage adjustments provided in the manufacturer's labeling. Use with caution; dosage reduction is necessary.
Moderate impairment (Child-Pugh class B): Continuous IV infusion: Initial: 0.5 mcg/kg/minute; measure aPTT after 2 hours and adjust dose as needed. In critically ill patients, consider measuring aPTT 2 hours after initiation, then every 4 hours to allow for steady state to be achieved. Adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value, not exceeding 100 seconds (Kiser 2011; Tardy-Poncet 2015).
Severe impairment (Child-Pugh class C): Continuous IV infusion: Initial: 0.25 mcg/kg/minute; measure aPTT after 2 hours and adjust dose as needed; in critically ill patients, consider measuring aPTT 2 hours after initiation, then every 4 hours to allow for steady state to be achieved. Adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value, not exceeding 100 seconds (Kiser 2011; Yarbrough 2012).
Percutaneous coronary intervention: Avoid use in patients with clinically significant hepatic impairment or elevations of ALT/AST ≥3 × ULN (has not been studied).
(For additional information see "Argatroban: Pediatric drug information")
Heparin-induced thrombocytopenia: Limited data available: Infants and Children ≤16 years: Note: Titration of maintenance dose must consider multiple factors including current argatroban dose, current aPTT, target aPTT, and clinical status of the patient. For specific uses, required maintenance dose is highly variable between patients. During the course of treatment, patient's dosing requirements may change as clinical status changes; critically ill patients and patients with hepatic dysfunction require lower dose; frequent dosage adjustments may be required in critical patients to maintain desired anticoagulant activity (Alsoufi 2004; Boshkov 2006; Keegan 2009). If argatroban therapy is used concurrently with or following FFP or a thrombolytic, some centers decrease dose by half (Alsoufi 2004).
Continuous IV infusion:
Initial dose: 0.75 mcg/kg/minute (Madabushi 2011)
Maintenance dose: Measure aPTT after 2 hours; adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value, not exceeding 100 seconds; adjust in increments of 0.1 to 0.25 mcg/kg/minute for normal hepatic function; reduce dose in hepatic impairment.
Note: A lower initial infusion rate may be needed in other pediatric patients with reduced clearance of argatroban (eg, patients with heart failure, multiple organ system failure, severe anasarca, postcardiac surgery or hepatic impairment). This precaution is based on adult studies of patients with these disease states who had reduced argatroban clearance.
Conversion to oral anticoagulant: Because there may be a combined effect on the INR when argatroban is combined with warfarin, loading doses of warfarin should not be used. Warfarin therapy should be started at the expected daily dose. Once combined INR on warfarin and argatroban is >4, stop argatroban. Repeat INR measurement in 4 to 6 hours; if INR is below therapeutic level, argatroban therapy may be restarted. Repeat procedure daily until desired INR on warfarin alone is obtained. Another option is to use factor X levels to monitor the effect of warfarin anticoagulation. When factor X level is <0.3, warfarin is considered therapeutic and at which time argatroban can be discontinued (Alsoufi 2004; Boshkov 2006).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to severe impairment: All patients: No dosage adjustment necessary.
Dialysis: Dialyzable, ~20% removed over 4 hours during hemodialysis (NCS/SCCM [Frontera 2016]); removal during hemodialysis and continuous venovenous hemofiltration did not alter clinical efficacy when used for anticoagulation in renal replacement therapy (Tang 2005)
Decreased clearance is seen with hepatic impairment; dose should be reduced.
Infants, Children, and Adolescents ≤16 years: Heparin-induced thrombocytopenia; IV continuous infusion:
Initial dose: 0.2 mcg/kg/minute (Young 2011)
Maintenance dose: Measure aPTT after 2 hours; adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value, not exceeding 100 seconds; adjust in increments of ≤0.05 mcg/kg/minute.
Refer to adult dosing.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, or 3 obesity (BMI ≥30 kg/m2): IV: Use actual body weight for initial weight-based dosing when used to treat thrombosis associated with heparin-induced thrombocytopenia or when used during percutaneous coronary intervention; titrate dose as usual based on either aPTT or ACT goals (expert opinion).
Rationale for recommendations: Pharmacokinetics and pharmacodynamic studies have not been evaluated prospectively in patients with obesity; however, retrospective data obtained in patients with a BMI up to 50 kg/m2 suggest using actual body weight to calculate weight-based doses, and that reduction of initial dose solely due to increased weight is unnecessary (Ansara 2009; Elagizi 2018; Hursting 2008; Rice 2007).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Generic: 50 mg/50 mL (50 mL); 250 mg/2.5 mL (2.5 mL); 125 mg/125 mL in NaCl 0.9% (125 mL [DSC]); 50 mg/50 mL in NaCl 0.9% (50 mL)
Solution, Intravenous [preservative free]:
Generic: 50 mg/50 mL (50 mL); 250 mg/2.5 mL (2.5 mL); 50 mg/50 mL in NaCl 0.9% (50 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 250 mg/2.5 mL (2.5 mL)
IV: The 2.5 mL (100 mg/mL) concentrated vial must be diluted to 1 mg/mL prior to administration. The premixed 50 mL or 125 mL vials and 250 mL bag (1 mg/mL) require no further dilution. The premixed 1 mg/mL vial may be inverted for use with an infusion set. For HIT, administer by continuous IV infusion. For PCI, administer by IV infusion and bolus (over 3 to 5 minutes through a large bore IV line).
IV: For IV use only. For HIT, administer by continuous IV infusion.
Note: Premixed solutions available.
IV infusion: 250 mg in 250 mL (concentration: 1000 mcg/mL) in D5W or NS
Note: Premixed solutions available.
IV infusion: 1000 mcg/mL
Heparin-induced thrombocytopenia: Prophylaxis or treatment of thrombosis in adults with heparin-induced thrombocytopenia (HIT).
Percutaneous coronary intervention: As an anticoagulant for percutaneous coronary intervention (PCI) in adults who have or are at risk of developing HIT.
Argatroban may be confused with Aggrastat, Orgaran
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
The Joint Commission (TJC) requires healthcare organizations that provide anticoagulant therapy to have approved protocols and evidence-based practice guidelines in place to reduce the risk of anticoagulant-associated patient harm. Patients receiving anticoagulants should receive individualized care through a defined process that includes medication selection, dosing (including adjustments for age, renal function, or liver function), drug-drug interactions, drug-food interactions, other applicable risk factors, monitoring, patient and family education, proper administration, reversal of anticoagulation, management of bleeding events, and perioperative management. This does not apply to routine short-term use of anticoagulants for prevention of venous thromboembolism during procedures or hospitalizations (NPSG.03.05.01).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions are reported for adults treated for heparin-induced thrombocytopenia (HIT) and percutaneous coronary intervention with or without heparin-induced thrombocytopenia (PCI), unless otherwise specified.
>10%:
Cardiovascular: Chest pain (PCI: 15%), hypotension (7% to 11%)
Gastrointestinal: Gastrointestinal hemorrhage (major: ≤2%; minor: Including hematemesis: HIT: 14%, PCI: ≤3%)
Genitourinary: Genitourinary tract hemorrhage (including hematuria; major: HIT: <1%; minor: HIT: 12%, PCI: 2%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (PCI: 4%), angina pectoris (PCI: 2%), brachial artery hemorrhage (minor: HIT: 2%), bradycardia (PCI: 5%), coronary occlusion (PCI: 2%), coronary thrombosis (PCI: 2%), ischemic heart disease (PCI: 2%), ventricular tachycardia (HIT: 5%)
Gastrointestinal: Abdominal pain (3% to 4%), diarrhea (HIT: 6%), nausea (5% to 7%), vomiting (4% to 6%)
Hematologic & oncologic: Decreased hematocrit (major: HIT: <1%; minor: HIT: ≤10%, PCI: ≤2%), decreased hemoglobin (major: HIT: <1%; minor: HIT: ≤10%, PCI: ≤2%), groin bleeding (including hematoma; minor: 4% to 5%), hemorrhage (major hemorrhage: HIT: 5%; minor: PCI [CABG related]: 2%)
Nervous system: Headache (PCI: 5%), pain (HIT: 5%)
Neuromuscular & skeletal: Back pain (PCI: 8%)
Respiratory: Cough (HIT: 3%), hemoptysis (minor: ≤3%)
Miscellaneous: Fever (≤7%)
<1%:
Cardiovascular: Aortic valve stenosis (PCI), atrial thrombosis (PCI), vascular disease (PCI)
Gastrointestinal: Gastroesophageal reflux disease (PCI)
Hematologic & oncologic: Disseminated intravascular coagulation (HIT), retroperitoneal bleeding (PCI)
Local: Bleeding at injection site (access site: PCI), local hemorrhage (limb and below-the-knee stump: HIT)
Nervous system: Cerebrovascular disease (PCI)
Respiratory: Pulmonary edema (PCI)
Frequency not defined: Hypersensitivity: Hypersensitivity reaction
Hypersensitivity to argatroban or any component of the formulation; major bleeding.
Canadian labeling: Additional contraindications (not in US labeling): Hereditary fructose intolerance.
Concerns related to adverse effects:
• Bleeding: The most common complication is bleeding and can occur at any site in the body. Use extreme caution in patients with hematologic conditions associated with increased bleeding (eg, congenital or acquired bleeding disorders, GI lesions); recent puncture of large vessels or organ biopsy; spinal anesthesia; immediately following lumbar puncture; recent cerebrovascular accident (CVA), stroke, intracerebral surgery, or other neuraxial procedure; severe hypertension; renal impairment; recent major surgery; recent major bleeding (intracranial, GI, intraocular, or pulmonary). Monitor for signs and symptoms of bleeding.
• Hypersensitivity: Airway, skin, and generalized hypersensitivity reactions have been reported.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage reduction is necessary; may require >4 hours to achieve full reversal of anticoagulant effects. Avoid use during PCI in patients with clinically significant hepatic impairment or elevations of ALT/AST ≥3 times ULN (has not been studied).
Special populations:
• Critically ill patients: Use with caution in critically-ill patients; reduced clearance may require dosage reduction.
The appropriate goals of anticoagulation and duration of treatment in pediatric patients have not been established. In pediatric trials, hypokalemia and abdominal pain were reported (Young 2007).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination
Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy
Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination
Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy
Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modification
Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Risk X: Avoid combination
Hemin: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Inotersen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Kanamycin: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid combination
Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination
Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Oritavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Risk C: Monitor therapy
Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination
Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Telavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Risk C: Monitor therapy
Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: Monitor for signs and symptoms of bleeding if these agents are combined. For the treatment of acute ischemic stroke, avoidance with anticoagulants is often recommended, see full Lexicomp or drug interaction monograph for details. Risk C: Monitor therapy
Tibolone: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Urokinase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid combination
Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Information related to argatroban in pregnancy is limited. Use of parenteral direct thrombin inhibitors in pregnancy should be limited to those women who have severe allergic reactions to heparin, including heparin-induced thrombocytopenia, and who cannot receive danaparoid (Guyatt 2012).
It is not known if argatroban is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Monitor hemoglobin, hematocrit, signs and symptoms of bleeding.
Heparin-induced thrombocytopenia: Obtain baseline aPTT prior to start of therapy. Check aPTT 2 hours after start of therapy (in critically ill patients, consider monitoring 2 hours after initiation then every 4 hours to allow for steady state to be achieved) to adjust dose, keeping the steady-state aPTT 1.5 to 3 times the initial baseline value (not exceeding 100 seconds).
Percutaneous coronary intervention: Monitor ACT before dosing, 5 to 10 minutes after bolus dosing, and after any change in infusion rate and at the end of the procedure. Additional ACT assessments should be made every 20 to 30 minutes during extended percutaneous coronary intervention procedures.
A direct, highly-selective thrombin inhibitor. Reversibly binds to the active thrombin site of free and clot-associated thrombin. Inhibits fibrin formation; activation of coagulation factors V, VIII, and XIII; activation of protein C; and platelet aggregation.
Onset of action: Immediate
Distribution: 174 mL/kg
Protein binding: Albumin: 20%; alpha1-acid glycoprotein: 34%
Metabolism: Hepatic via hydroxylation and aromatization (major route). Metabolism via CYP3A4/5 (minor route) to four metabolites. Unchanged argatroban is the major plasma component. Plasma concentration of metabolite M1 is 0% to 20% of the parent drug and is three- to five-fold weaker.
Half-life elimination: 39 to 51 minutes; Hepatic impairment: 181 minutes
Time to peak: Steady-state: 1 to 3 hours
Excretion: Feces (~65%; 14% unchanged); urine (~22%; 16% unchanged); low quantities of metabolites M2-4 in urine
Clearance:
Pediatric patients (seriously ill): 0.16 L/kg/hour; 50% lower than healthy adults
Pediatric patients (seriously ill with elevated bilirubin due to hepatic impairment or cardiac complications; n=4): 0.03 L/kg/hour; 80% lower than pediatric patients with normal bilirubin
Adult: 0.31 L/kg/hour (5.1 mL/kg/minute); hepatic impairment: 1.9 mL/kg/minute
Solution (Argatroban in Sodium Chloride Intravenous)
50 mg/50 mL 0.9% (per mL): $4.68 - $5.85
Solution (Argatroban Intravenous)
50 mg/50 mL (per mL): $2.40 - $4.75
250 mg/2.5 mL (per mL): $114.76 - $244.80
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