ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Argatroban: Drug information

Argatroban: Drug information
(For additional information see "Argatroban: Patient drug information" and see "Argatroban: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Pharmacologic Category
  • Anticoagulant;
  • Anticoagulant, Direct Thrombin Inhibitor
Dosing: Adult
Heparin-induced thrombocytopenia

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

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.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: IV: No dosage adjustment necessary for any degree of kidney dysfunction (Hursting 2008b; Swan 2000).

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):

Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).

IV: No data; no dosage adjustment necessary (expert opinion).

Hemodialysis, intermittent (thrice weekly): Not significantly dialyzable: Dialytic clearance increases systemic clearance 20% during the procedure without any significant impact on clotting measures (activated clotting time [ACT]) (Murray 2004; Tang 2005).

IV: No dosage adjustment or supplemental dose necessary (Hursting 2008b; Murray 2004; Reddy 2005; Tang 2005).

Peritoneal dialysis: Unlikely to be significantly dialyzable (expert opinion):

IV: No dosage adjustment necessary (Reddy 2005; expert opinion).

CRRT: IV: No dosage adjustment necessary (Reddy 2005; Tang 2005).

PIRRT (eg, sustained, low-efficiency diafiltration): IV: No dosage adjustment necessary (expert opinion).

Dosing: Hepatic Impairment: Adult

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).

Dosing: Obesity: Adult

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 2008a; Rice 2007).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Argatroban: Pediatric drug information")

Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT): Limited data available: Note: Required maintenance dose is highly variable between patients; frequent dosage adjustments required in critically ill patients and/or patients with liver impairment to maintain desired anticoagulant activity.

Infants, Children, and Adolescents ≤16 years: Continuous IV infusion:

Initial dose: 0.75 mcg/kg/minute; measure aPTT after 2 hours; titrate to maintain aPTT in desired range; adjust in increments of 0.1 to 0.25 mcg/kg/minute for normal hepatic function; dosing based on population modeling and simulations (Radulescu 2017; Young 2011). Note: A lower initial infusion rate may be needed for critically ill patients and/or patients with liver impairment.

Maintenance dose: Measure aPTT 2 hours after any dose change and at least once daily; more frequent monitoring may be required based on clinical status; adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value (depends on bleeding risk), 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 (Young 2011; manufacturer's labeling).

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).

Anticoagulation, mechanical circulatory support

Anticoagulation, mechanical circulatory support:

Ventricular assist device (VAD) (ACTION 2020): Very limited data available:

Note: Dosing based on a consensus protocol; goal aPTT range determined by risk of bleeding and thrombosis and postoperative phase of care.

Infants, Children, and Adolescents: Initial dose: Continuous IV infusion: 0.5 mcg/kg/minute; consider a lower initial dose in the setting of hepatic dysfunction with baseline elevated INR; titrate to achieve target aPTT (See "Dose Adjustments to Achieve Target aPTT" table); usual dosage range: 1 to 5 mcg/kg/minute; doses up to 8 mcg/kg/minute have been used; maximum adult dose: 10 mcg/kg/minute.

Dose Adjustments to Achieve Target aPTT

aPTT

Argatroban titration

Time to repeat aPTTa

a Consider more frequent aPTT monitoring based on clinical scenario.

b Round dose up to closest second decimal (hundredth place).

c Recommendation in patient with normal hepatic function; in patients with significant hepatic impairment, hold infusion for 2 hours then recheck aPTT before restarting (see "Dosing: Hepatic Impairment: Pediatric").

Adapted from ACTION 2020.

≥15 to 30 seconds below goal range

Increase infusion by 25%b

2 to 3 hours

5 to <15 seconds below goal range

Increase infusion by 15%b

2 to 3 hours

Within goal range

No change

2 to 3 hours; then daily after 2 consecutive aPTTs within goal range

5 to <15 seconds above goal range

Decrease infusion by 15%b

2 to 3 hours

≥15 to 30 seconds above goal range

Decrease infusion by 25%b

2 to 3 hours

>3× baseline or >~120 seconds

Hold infusion for 15 minutes and decrease infusion by 30%c

2 hours

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Mild to severe impairment: There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; however, based on consensus protocol and adult information, no dosage adjustment necessary (ACTION 2020).

Dialysis: Based on adult information, ~20% argatroban 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).

Dosing: Hepatic Impairment: Pediatric

There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; decreased clearance has been reported in pediatric patients with liver impairment; the dose should be reduced:

Heparin-induced thrombocytopenia (HIT):

Infants, Children, and Adolescents ≤16 years:

AST/ALT ≥3 times ULN:

Initial dose: Continuous IV Infusion: Reduce initial dose to 0.2 mcg/kg/minute; measure aPTT after 2 hours and adjust dose to maintain aPTT in the desired range; adjust in increments of ≤0.05 mcg/kg/minute (Young 2011).

Maintenance dose: Measure aPTT 2 hours after any dose change and at least once daily; more frequent monitoring may be required based on clinical status; adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value (depends on bleeding risk), not exceeding 100 seconds; adjust in increments of ≤0.05 mcg/kg/minute (Young 2011; manufacturer's labeling).

Ventricular assist device (VAD):

Infants, Children, and Adolescents: Continuous IV Infusion (ACTION 2020):

Baseline liver impairment:

Initial dose: Consider dosage reduction if known impairment and baseline elevated INR.

Liver impairment during treatment:

Maintenance dose: Check aPTT and monitor closely.

Significant liver impairment during treatment:

aPTT >3 times baseline or >~120 seconds: Hold infusion for 2 hours then recheck aPTT before restarting.

Adverse Reactions

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

Contraindications

Hypersensitivity to argatroban or any component of the formulation; major bleeding.

Canadian labeling: Additional contraindications (not in US labeling): Hereditary fructose intolerance.

Warnings/Precautions

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.

Dosage Forms: US

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); 50 mg/50 mL in NaCl 0.9% (50 mL)

Generic Equivalent Available: US

Yes

Pricing: US

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

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 250 mg/2.5 mL (2.5 mL)

Administration: Adult

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).

Administration: Pediatric

Parenteral: Continuous IV infusion: Vials (concentrated solution) must be diluted prior to administration; premixed IV solution (1 mg/mL) is available. Administer as a continuous IV infusion with the use of an infusion pump.

Usual Infusion Concentrations: Adult

Note: Premixed solutions available.

IV infusion: 250 mg in 250 mL (concentration: 1000 mcg/mL) in D5W or NS

Usual Infusion Concentrations: Pediatric

Note: Premixed solutions available.

IV infusion: 1 mg/mL.

Use: Labeled Indications

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.

Medication Safety Issues
Sound-alike/look-alike issues:

Argatroban may be confused with Aggrastat, Orgaran

High alert medication:

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.

National Patient Safety Goals:

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).

Metabolism/Transport Effects

None known.

Drug Interactions

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

Anacaulase: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Anagrelide: 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

Defibrotide: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

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

Lecanemab: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of hemorrhage may be increased. 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 (Ophthalmic): 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

Pirtobrutinib: 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

Protein C Concentrate (Human): May enhance the anticoagulant effect of Anticoagulants. 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 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

Pregnancy Considerations

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).

Breastfeeding Considerations

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.

Monitoring Parameters

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.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Exembol;
  • (AT) Austria: Argatra | Argatroban accord;
  • (CH) Switzerland: Argatra;
  • (DE) Germany: Argatra | Argatroban accord;
  • (EE) Estonia: Exembol multidose;
  • (ES) Spain: Arganova;
  • (FI) Finland: Novastan;
  • (FR) France: Arganova | Argatroban accord;
  • (GB) United Kingdom: Exembol;
  • (IT) Italy: Novastan;
  • (JP) Japan: Slonnon Hi;
  • (LT) Lithuania: Argatra;
  • (NL) Netherlands: Arganova | Arganova multidose;
  • (NO) Norway: Argatra;
  • (PL) Poland: Argatra;
  • (SE) Sweden: Novastan
  1. Advanced Cardiac Therapies Improving Outcomes Network (ACTION). Direct thrombin inhibitor (DTI) harmonization protocol for VADs. https://www.actionlearningnetwork.org. Updated August 24, 2020. Accessed January 2023.
  2. Alsoufi B, Boshkov LK, Kirby A, et al. Heparin-induced thrombocytopenia (HIT) in pediatric cardiac surgery: an emerging cause of morbidity and mortality. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2004;7:155-171. [PubMed 15283365]
  3. American Society of Health-System Pharmacists (ASHP). Pediatric continuous infusion standards. Available at https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/Pediatric-Infusion-Standards.ashx. Updated January 2021. Accessed June 18, 2021.
  4. Ansara AJ, Arif S, Warhurst RD. Weight-based argatroban dosing nomogram for treatment of heparin-induced thrombocytopenia. Ann Pharmacother. 2009;43(1):9-18. doi:10.1345/aph.1L213 [PubMed 19126826]
  5. Argatroban 250 mg per 250 mL [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA Inc; August 2017.
  6. Argatroban injection 125 mg per 125 mL dextrose [prescribing information]. Princeton, NJ: Sandoz Inc; April 2019.
  7. Argatroban injection 250 mg per 2.5 mL [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc; July 2019.
  8. Argatroban injection 50 mg per 50 mL (1 mg per mL) [prescribing information]. Schaumburg, IL: Sagent Pharmaceuticals; March 2021.
  9. Argatroban injection [prescribing information]. Eatontown, NJ: Hikma Pharmaceuticals USA Inc; January 2020.
  10. Argatroban injection [product monograph]. Boucherville, Quebec, Canada: Sandoz Canada Inc; April 2020.
  11. Argatroban solution 50 mg per 50 mL [prescribing information]. Princeton, NJ: Sandoz Inc; June 2018.
  12. Arpino PA, Demirjian Z, and Van Cott EM, “Use of the Chromogenic Factor X Assay to Predict the International Normalized Ratio in Patients Transitioning from Argatroban to Warfarin,” Pharmacotherapy, 2005, 25(2):157-64. [PubMed 15767231]
  13. Baghdasarian SB, Singh I, Militello MA, et al, “Argatroban Dosage in Critically Ill Patients With HIT,” Blood 2004, 104:1779 [abstract 1779 from 2004 ASH Annual Meeting].
  14. Beiderlinden M, Treschan TA, Gorlinger K, et al. Argatroban anticoagulation in critically ill patients. Ann Pharmacother. 2007;41(5):749-754. [PubMed 17440009]
  15. Bilbao-Meseguer I, Rodríguez-Gascón A, Barrasa H, Isla A, Solinís MÁ. Augmented renal clearance in critically ill patients: a systematic review. Clin Pharmacokinet. 2018;57(9):1107-1121. doi:10.1007/s40262-018-0636-7 [PubMed 29441476]
  16. Boshkov LK, Kirby A, Shen I, et al. Recognition and management of heparin-induced thrombocytopenia in pediatric cardiopulmonary bypass patients. Ann Thorac Surg. 2006;81(6):S2355-S2359. [PubMed 16731103]
  17. Dager WE, Gulseth MP, Nutescu EA, eds. Anticoagulation Therapy: A Clinical Practice Guide. 2nd ed. American Society of Health-System Pharmacists; 2018.
  18. Dager WE, White RH. Pharmacotherapy of heparin-induced thrombocytopenia. Expert Opin Pharmacother. 2003;4(6):919-940. [PubMed 12783589]
  19. de Denus S and Spinler SA, “Decreased Argatroban Clearance Unaffected by Hemodialysis in Anasarca,” Ann Pharmacother, 2003, 37(9):1237-40. [PubMed 12921506]
  20. Elagizi S, Davis K. Argatroban dosing in obesity. Thromb Res. 2018;163:60-63. doi:10.1016/j.thromres.2018.01.011 [PubMed 29367082]
  21. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  22. Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al; Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6-46. [PubMed 26714677]
  23. Garcia DA, Baglin TP, Weitz JI, et al, “Parenteral Anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines,” Chest, 2012, 141(2 Suppl):24-43. [PubMed 22315264]
  24. Guyatt GH, Akl EA, Crowther M, et al, “Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines,” Chest, 2012, 141(2 Suppl):7-47. [PubMed 22315257]
  25. Hirsh J, Guyatt G, Albers GW, et al, “Executive Summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition),” Chest, 2008, 133(6 Suppl):71-109. [PubMed 18574259]
  26. Honisko ME, Fink JM, Militello MA, et al, “Compatibility of Argatroban With Selected Cardiovascular Agents,” Am J Health Syst Pharm, 2004, 61(22):2415-8. [PubMed 15581266]
  27. Hursting MJ, Jang IK. Effect of body mass index on Argatroban therapy during percutaneous coronary intervention. J Thromb Thrombolysis. 2008a;25(3):273-279. doi:10.1007/s11239-007-0051-7 [PubMed 17530465]
  28. Hursting MJ, Murray PT. Argatroban anticoagulation in renal dysfunction: a literature analysis. Nephron Clin Pract. 2008b;109(2):c80-c94. doi:10.1159/000139993 [PubMed 18560242]
  29. Kiser TH, Jung R, MacLaren R, Fish DN. Evaluation of diagnostic tests and argatroban or lepirudin therapy in patients with suspected heparin-induced thrombocytopenia. Pharmacotherapy. 2005;25(12):1736-1745. doi:10.1592/phco.2005.25.12.1736 [PubMed 16305293]
  30. Kiser TH, Mann AM, Trujillo TC, Hassell KL. Evaluation of empiric versus nomogram-based direct thrombin inhibitor management in patients with suspected heparin-induced thrombocytopenia. Am J Hematol. 2011;86(3):267-272. doi:10.1002/ajh.21955 [PubMed 21328434]
  31. Levine RL, Hursting MJ, and McCollum D, "Argatroban Therapy in Heparin-Induced Thrombocytopenia With Hepatic Dysfunction," Chest, 2006, 129(5):1167-75. [PubMed 16685006]
  32. Lewis BE, Matthai WH, Cohen M, et al, “Argatroban Anticoagulation During Percutaneous Coronary Intervention in Patients With Heparin-Induced Thrombocytopenia,” Catheter Cardiovasc Interv, 2002, 57(2):177-84. [PubMed 12357516]
  33. Lewis BE, Wallis DE, Berkowitz SD, et al, “Argatroban Anticoagulant Therapy in Patients With Heparin-Induced Thrombocytopenia,” Circulation, 2001, 103(14):1838-43. [PubMed 11294800]
  34. Link A, Girndt M, Selejan S, et al, “Argatroban for Anticoagulation in Continuous Renal Replacement Therapy,” Crit Care Med, 2009, 37(1):105-10. [PubMed 19050602]
  35. Linkins L, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl):e495-e530. [PubMed 22315270]
  36. Murray PT, Reddy BV, Grossman EJ, et al. A prospective comparison of three argatroban treatment regimens during hemodialysis in end-stage renal disease. Kidney Int. 2004;66(6):2446-2453. doi:10.1111/j.1523-1755.2004.66022.x [PubMed 15569338]
  37. Radulescu VC. Anticoagulation therapy in children. Semin Thromb Hemost. 2017;43(8):877-885. doi:10.1055/s-0036-1598004 [PubMed 28346967]
  38. Reddy BV, Grossman EJ, Trevino SA, Hursting MJ, Murray PT. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia requiring renal replacement therapy. Ann Pharmacother. 2005;39(10):1601-1605. doi:10.1345/aph.1G033 [PubMed 16131539]
  39. Reichert MG, MacGregor DA, Kincaid EH, et al, “ Excessive Argatroban Anticoagulation for Heparin-Induced Thrombocytopenia,” Ann Pharmacother, 2003, 37(5):652-4. [PubMed 12708939]
  40. Rice L, Hursting MJ, Baillie GM, McCollum DA. Argatroban anticoagulation in obese versus nonobese patients: implications for treating heparin-induced thrombocytopenia. J Clin Pharmacol. 2007;47(8):1028-1034. doi:10.1177/0091270007302951 [PubMed 17525167]
  41. Swan SK, Hursting MJ. The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender, and hepatic or renal dysfunction. Pharmacotherapy. 2000;20(3):318-329. doi:10.1592/phco.20.4.318.34881 [PubMed 10730687]
  42. Tang IY, Cox DS, Patel K, et al. Argatroban and renal replacement therapy in patients with heparin-induced thrombocytopenia. Ann Pharmacother. 2005;39(2):231-236. doi:10.1345/aph.1E480 [PubMed 15632219]
  43. Tardy-Poncet B, Nguyen P, Thiranos JC, et al. Argatroban in the management of heparin-induced thrombocytopenia: a multicenter clinical trial. Crit Care. 2015;19:396. doi:10.1186/s13054-015-1109-0 [PubMed 26556106]
  44. Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49(1):1-16. doi:10.2165/11318140-000000000-00000 [PubMed 26556106]
  45. Yarbrough PM, Varedi A, Walker A, et al. Argatroban dose reductions for suspected heparin-induced thrombocytopenia complicated by Child-Pugh class C liver disease. Ann Pharmacother. 2012;46(11):e30. [PubMed 23073302]
  46. Young G and Boshkov L. Prospective study of direct thrombin inhibition with argatroban in pediatric patients requiring non-heparin anticoagulation. Blood. 2007; 110.
  47. Young G, Boshkov LK, Sullivan JE, et al. Argatroban therapy in pediatric patients requiring nonheparin anticoagulation: an open-label, safety, efficacy, and pharmacokinetic study. Pediatr Blood Cancer. 2011;56(7):1103-1109. [PubMed 21488155]
Topic 8765 Version 331.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟