Safety and effectiveness have not been established in pediatric patients. 

Argatroban was studied among 18 seriously ill pediatric patients who required an alternative to heparin anticoagulation. Most patients were diagnosed with HIT or suspected HIT. Age ranges of patients were <6 months, n = 8; six months to <8 years, n = 6; 8 to 16 years, n = 4. All patients had serious underlying conditions and were receiving multiple concomitant medications. Thirteen patients received argatroban solely as a continuous infusion (no bolus dose). Dosing was initiated in the majority of these 13 patients at 1 mcg/kg/min. Dosing was titrated as needed to achieve and maintain an aPTT of 1.5 to 3 times the baseline value. Most patients required multiple dose adjustments to maintain anticoagulation parameters within the desired range. During the 30-day study period, thrombotic events occurred during argatroban administration to two patients and following argatroban discontinuation in three other patients. Major bleeding occurred among two patients: one patient experienced an intracranial hemorrhage after 4 days of argatroban therapy in the setting of sepsis and thrombocytopenia and another patient experienced an intracranial hemorrhage after receiving argatroban for greater than 14 days. The study findings did not establish the safe and effective use of argatroban in pediatric patients and the dosing of 1 mcg/kg/min was not supported by the pharmacokinetic data described below. 

Pediatric Pharmacokinetics (PK) and Pharmacodynamics (PD) 

PK parameters of argatroban were characterized in population PK/PD analysis model with sparse data from 15 seriously ill pediatric patients. Argatroban clearance in these seriously ill pediatric patients (0.16 L/hr/kg) was 50% lower compared to argatroban clearance in healthy adults (0.31 L/hr/kg). Four pediatric patients with elevated bilirubin (secondary to cardiac complications or hepatic impairment) had, on average, 80% lower clearance (0.03 L/hr/kg) when compared to pediatric patients with normal bilirubin levels.

These PK/PD analysis models based on a goal of aPTT prolongation of 1.5 to 3 times the baseline value and avoidance of an aPTT >100 seconds for seriously ill pediatric patients with HIT/HITTS who require an alternative to heparin suggested the following:  


  * For patients with normal hepatic function, a starting infusion rate of 0.75 mcg/kg/min may have comparable aPTT responses as a starting dose of 2 mcg/kg/min in healthy adults. Additionally, based on an evaluation of aPTT every two hours, increasing the dosage by 0.1 to 0.25 mcg/kg/min could achieve additional aPTT responses. 
  * For patients with hepatic impairment a starting infusion rate of 0.2 mcg/kg/min with increasing dosing by increments of 0.05 mcg/kg/min may have comparable argatroban exposure as expected with adult doses. 



The safety and effectiveness of argatroban with the above dosing have not been adequately assessed in pediatric patients and the safety and effectiveness of argatroban is not established in pediatric patients. In addition, the described dosage did not take into account multiple factors that could affect the dosage such as current aPTT, target aPTT, and the clinical status of the patient.