Argatroban (argatroban)

ACCP suggests a reduced dosage of argatroban for the treatment of HIT/HITTS in patients with heart failure, multiple organ system failure, or severe anasarca, and for patients following cardiac surgery. ACCP suggests an initial infusion rate of 0.5-1.2 mcg/kg per minute due to an increased risk of bleeding in these patient populations.

No dosage adjustment is necessary in geriatric patients.

Use of argatroban in patients with hepatic impairment requires dosage reduction and careful monitoring of the aPTT. For adults with HIT/HITTS and moderate or severe hepatic impairment (based on Child-Pugh classification), an initial dosage of 0.5 mcg/kg per minute is recommended based on an approximate fourfold decrease in argatroban clearance relative to that in individuals with normal hepatic function. Subsequent dosage may then be adjusted as clinically indicated. Patients with hepatic impairment may require a longer time and more dosage adjustments to achieve steady-state aPTT concentrations. Use of high dosages of argatroban should be avoided in patients undergoing PCI who have clinically important hepatic disease or serum AST or ALT elevations 3 times the upper limit of normal or higher because such patients have not been studied in clinical trials with the drug.

The manufacturer does not make any dosing recommendations specific to obesity. Argatroban dosing requirements in obese versus nonobese patients were evaluated in a small, single-center, retrospective study; the study included 121 patients with suspected HIT who received argatroban for at least 12 hours. Patients with a body mass index (BMI) >30 kg/m2 were compared with patients with a BMI <=30 kg/m2. No meaningful differences were observed in median maintenance dosage requirements, thrombosis events, or in-hospital major bleeding between the patients. Based on these findings, the authors suggest that argatroban dosing be based on actual body weight in obese patients.

No dosage adjustment is necessary in patients with impaired renal function.

Argatroban is administered by continuous IV infusion. The drug is commercially available as a 100-mg/mL injection concentrate, and also available as 1-mg/mL ready-to-use preparations.

The commercially available injection concentrate (100 mg/mL) must be diluted 100-fold in 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer's injection to a final concentration of 1 mg/mL prior to administration. The solution should be mixed by repeated inversion of the IV container for 1 minute. The argatroban IV solution may be slightly hazy just after preparation because of the formation of microprecipitates that rapidly dissolve upon further mixing. Exposure to cold temperatures may slow the rate of dissolution. The solution should be clear prior to use. Properly prepared diluted solutions of argatroban are stable for 24 hours at room temperature when exposed to ambient indoor light, or for 96 hours at room temperature or under refrigeration when protected from light. Argatroban solutions should not be exposed to direct sunlight.

Commercially available 1-mg/mL ready-to-use preparations of argatroban are available in single-dose 50 mL or 125 mL vials; dilution of these preparations is not required. The vials may be inverted for use with a medical infusion set. The drug should not be used if the solution is cloudy or contains visible particulates.

Before administering argatroban, all parenteral anticoagulants must be discontinued and a baseline activated partial thromboplastin time (aPTT) obtained.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Major bleeding.

*History of hypersensitivity to argatroban or any ingredient(s) in the formulation.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

In patients receiving argatroban for the treatment of HIT/HITTS, the most common adverse effects (occurring in >5% of patients) were dyspnea, hypotension, fever, diarrhea, sepsis, and cardiac arrest.

In patients receiving argatroban for PCI, the most common adverse effects (occurring in >5% of patients) were chest pain, hypotension, back pain, nausea, vomiting, and headache.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy of argatroban have not been fully established in pediatric patients; however, the drug has been evaluated in a limited number of seriously ill pediatric patients <16 years of age with HIT or HITTS. In a small, multicenter open-label study, 18 seriously ill pediatric patients with a clinical condition requiring alternative nonheparin anticoagulation received argatroban at an initial dosage of 1 mcg/kg per minute titrated to maintain a target aPTT of 1.5-3 times the baseline value. During the 30-day study period, thrombotic events occurred in 5 patients and major bleeding (intracranial hemorrhage) was reported in 2 patients. All of the patients had serious comorbid conditions and were receiving multiple concomitant medications; most were diagnosed with documented or suspected HIT. In a pharmacokinetic/pharmacodynamic analysis model using data from 15 seriously ill pediatric patients, argatroban clearance was reduced by 50% in these patients compared with healthy adults and by approximately 80% in pediatric patients with elevated bilirubin concentrations compared to pediatric patients with normal bilirubin concentrations. Based on these findings and an aPTT goal of 1.5-3 times the baseline value (without exceeding aPTT of 100 seconds), a dosage regimen has been suggested for seriously ill pediatric patients with HIT/HITTS who require an alternative to heparin.

Available data do not support an association between argatroban and adverse fetal outcomes. Women with underlying thromboembolic disease and certain high-risk pregnancy conditions have an increased risk of thromboembolism during pregnancy. Data show that women with a history of venous thrombosis have a high risk for recurrence during pregnancy. The risk of untreated thromboembolism in the mother should be assessed against the risk of hemorrhage in the mother and fetus when considering the use of anticoagulants, including argatroban.

Argatroban is distributed into milk in rats; it is not known whether the drug is distributed into human milk. It is not known whether argatroban affects the breast-fed child or affects milk production. The benefits of breast-feeding should be considered along with the importance of the drug to the woman and any potential adverse effects on the breast-fed child from the drug or underlying maternal condition.

About one-third of patients in clinical studies of argatroban were >=65 years of age. No substantial differences in efficacy or safety have been observed relative to younger adults. A safety analysis suggested an increased trend for adverse events in older patients, but it was unclear whether this was due to the greater prevalence of underlying conditions predisposing these patients to adverse reactions or to a different safety profile of argatroban in older patients.