ARGATROBAN

ARGATROBAN- argatroban injection
Accord Healthcare Inc.

1 INDICATIONS AND USAGE

1.1 Heparin-Induced Thrombocytopenia

Argatroban in Sodium Chloride Injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT).

1.2 Percutaneous Coronary Intervention

Argatroban in Sodium Chloride Injection is indicated as an anticoagulant in adult patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI).

2 DOSAGE AND ADMINISTRATION

2.1 Preparation for Intravenous Administration

Each 50 mL glass vial contains 50 mg of argatroban (1 mg/mL); and, as supplied, is ready for intravenous infusion. Dilution is not required.

Argatroban in Sodium Chloride 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 the solution is cloudy, contains precipitates, or if the flip off seal is not intact.

Vial may be inverted for use with a medical infusion set.

2.2 Dosing in Patients with Heparin-Induced Thrombocytopenia

Initial Dosage

Before administering Argatroban in Sodium Chloride Injection, discontinue heparin therapy and obtain a baseline aPTT. The recommended initial dose of Argatroban in Sodium Chloride Injection for adult patients without hepatic impairment is 2 mcg/kg/min, administered as a continuous infusion (see Table 1).

*with or without thrombosis
Table 1. Recommended Doses and Infusion Rates for 2 mcg/kg/min Dose of Argatroban in Sodium Chloride Injection for Patients with HIT* and without Hepatic Impairment (1 mg/mL Concentration)
Body Weight (kg)	Dose (mcg/min)	Infusion Rate (mL/hr)
50	100	6
60	120	7
70	140	8
80	160	10
90	180	11
100	200	12
110	220	13
120	240	14
130	260	16
140	280	17

Monitoring Therapy

For use in HIT, therapy with Argatroban in Sodium Chloride 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 in Sodium Chloride 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.

Dosage Adjustment

After the initiation of Argatroban in Sodium Chloride 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)] .

2.3 Dosing in Patients Undergoing Percutaneous Coronary Interventions

Initial Dosage

Initiate an infusion of Argatroban in Sodium Chloride 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.

Dosage Adjustment

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).

If the ACT is greater than 450 seconds, decrease the infusion rate to 15 mcg/kg/min, and check the ACT 5 to 10 minutes later ( Table 3).

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.

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.

NOTE: 1 mg = 1000 mcg; 1 kg = 2.2 lbs
Table 2. Recommended Starting and Maintenance Doses (Within the Target ACT Range) of Argatroban in Sodium Chloride Injection in Patients Undergoing PCI without Hepatic Impairment (1 mg/mL Concentration)
Body Weight (kg)	Starting Bolus Dose (350 mcg/kg)		Starting and Maintenance Continuous Infusion Dosing For ACT 300-450 seconds 25 mcg/kg/min
	Bolus Dose (mcg)	Bolus Volume (mL)	Continuous Infusion Dose (mcg/min)	Continuous Infusion Rate (mL/hr)
50	17,500	18	1,250	75
60	21,000	21	1,500	90
70	24,500	25	1,750	105
80	28,000	28	2,000	120
90	31,500	32	2,250	135
100	35,000	35	2,500	150
110	38,500	39	2,750	165
120	42,000	42	3,000	180
130	45,500	46	3,250	195
140	49,000	49	3,500	210

NOTE: 1 mg = 1000 mcg; 1 kg = 2.2 lbs † Additional intravenous bolus dose of 150 mcg/kg should be administered if ACT less than 300 seconds. * No bolus dose is given if ACT greater than 450 seconds.
Table 3. Recommended Dose Adjustments of Argatroban in Sodium Chloride Injection for Patients Outside of ACT Target Range Undergoing PCI without Hepatic Impairment (1 mg/mL Concentration)
Body Weight (kg)	If ACT Less than 300 seconds Dosage Adjustment † 30 mcg/kg/min				If ACT Greater than 450 seconds Dosage Adjustment* 15 mcg/kg/min
	Additional Bolus Dose (mcg)	Bolus Volume (mL)	Continuous Infusion Dose (mcg/min)	Continuous Infusion Rate (mL/hr)	Continuous Infusion Dose (mcg/min)	Continuous Infusion Rate (mL/hr)
50	7,500	8	1,500	90	750	45
60	9,000	9	1,800	108	900	54
70	10,500	11	2,100	126	1,050	63
80	12,000	12	2,400	144	1,200	72
90	13,500	14	2,700	162	1,350	81
100	15,000	15	3,000	180	1,500	90
110	16,500	17	3,300	198	1,650	99
120	18,000	18	3,600	216	1,800	108
130	19,500	20	3,900	234	1,950	117
140	21,000	21	4,200	252	2,100	126

Monitoring Therapy

For use in PCI, therapy with Argatroban in Sodium Chloride 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.

Continued Anticoagulation after PCI

If a patient requires anticoagulation after the procedure, Argatroban in Sodium Chloride 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 (2.2)] .