ARGATROBAN

ARGATROBAN — argatroban injection
Caplin Steriles Limited

1 INDICATIONS & USAGE

1.1 Heparin-Induced Thrombocytopenia

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

1.2 Percutaneous Coronary Intervention

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

2 DOSAGE & ADMINISTRATION

2.1 Preparation for Intravenous Administration

Dilution is not required for Argatroban Injection 50 mg/50 mL (1 mg/mL).
Argatroban Injection 50 mg/50 mL (1 mg/mL)

Each 50 mL glass vial contains 50 mg argatroban (1 mg/mL); and, as supplied, is ready for intravenous infusion. Dilution is not required. Argatroban 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 solution is cloudy, contains precipitates, or if the flip off seals 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, discontinue heparin therapy and obtain a baseline activated partial thromboplastin time (aPTT). The recommended initial dose of argatroban for adult patients without hepatic impairment is 2 mcg/kg/min, administered as a continuous infusion (see Table 1).

Table 1 Recommended Doses and Infusion Rates for 2 mcg/kg/min Dose of Argatroban for Patients With] HIT* and Without Hepatic Impairment (1 mg/mL Final 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

*with or without thrombosis

Monitoring Therapy

For use in HIT, therapy with Argatroban 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 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 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 Intervention

Initial Dosage
Initiate an infusion of Argatroban 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.

Table 2. Recommended Starting and Maintenance Doses (Within the Target ACT Range) of Argatroban Injection in Patients Undergoing PCI Without Hepatic Impairment (1 mg/mL Final 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	17500	18	1250	75
60	21000	21	1500	90
70	24500	25	1750	105
80	28000	28	2000	120
90	31500	32	2250	135
100	35000	35	2500	150
110	38500	39	2750	165
120	42000	42	3000	180
130	45500	46	3250	195
140	49000	49	3500	210

NOTE: 1 mg = 1000 mcg; 1 kg = 2.2 lbs

Table 3. Recommended Dose Adjustments of Argatroban Injection for Patients Outside of ACT Target Range Undergoing PCI Without Hepatic Impairment (1 mg/mL Final 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	7500	8	1500		90	750	45
60	9000	9	1800	108		900	54
70	10500	11	2100	126		1050	63
80	12000	12	2400	144		1200	72
90	13500	14	2700	162		1350	81
100	15000	15	3000	180		1500	90
110	16500	17	3300	198		1650	99
120	18000	18	3600	216		1800	108
130	19500	20	3900	234		1950	117
140	21000	21	4200	252		2100	126

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

Monitoring Therapy
For use in PCI, therapy with Argatroban 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 prolonged procedure.

Continued Anticoagulation after PCI
If a patient requires anticoagulation after the procedure, Argatroban 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 (2.1) ].