ARGATROBAN (Page 6 of 6)

14.2 Percutaneous Coronary Intervention (PCI) Patients with or at Risk for HIT

In 3 similarly designed trials, argatroban was administered to 91 patients with current or previous clinical diagnosis of HIT or heparin-dependent antibodies, who underwent a total of 112 percutaneous coronary interventions (PCIs) including percutaneous transluminal coronary angioplasty (PTCA), coronary stent placement, or atherectomy. Among the 91 patients undergoing their first PCI with argatroban, notable ongoing or recent medical history included myocardial infarction (n = 35), unstable angina (n = 23), and chronic angina (n = 34). There were 33 females and 58 males. The average age was 67.6 years (median 70.7, range 44 to 86), and the average weight was 82.5 kg (median 81 kg, range 49 to 141).

Twenty-one of the 91 patients had a repeat PCI using argatroban an average of 150 days after their initial PCI. Seven of 91 patients received glycoprotein IIb/IIIa inhibitors. Safety and efficacy were assessed against historical control populations who had been anticoagulated with heparin.

All patients received oral aspirin (325 mg) 2 to 24 hours prior to the interventional procedure. After venous or arterial sheaths were in place, anticoagulation was initiated with a bolus of argatroban of 350 mcg/kg via a large-bore intravenous line or through the venous sheath over 3 to 5 minutes. Simultaneously, a maintenance infusion of 25 mcg/kg/min was initiated to achieve a therapeutic activated clotting time (ACT) of 300 to 450 seconds. If necessary to achieve this therapeutic range, the maintenance infusion dose was titrated (15 to 40 mcg/kg/min) and/or an additional bolus dose of 150 mcg/kg could be given. Each patient’s ACT was checked 5 to 10 minutes following the bolus dose. The ACT was checked as clinically indicated. Arterial and venous sheaths were removed no sooner than 2 hours after discontinuation of argatroban and when the ACT was less than 160 seconds.

If a patient required anticoagulation after the procedure, argatroban could be continued, but at a lower infusion dose between 2.5 and 5 mcg/kg/min. An aPTT was drawn 2 hours after this dose reduction and the dose of argatroban then was adjusted as clinically indicated (not to exceed 10 mcg/kg/min), to reach an aPTT between 1.5 and 3 times baseline value (not to exceed 100 seconds).

In 92 of the 112 interventions (82%), the patient received the initial bolus of 350 mcg/kg and an initial infusion dose of 25 mcg/kg/min. The majority of patients did not require additional bolus dosing during the PCI procedure. The mean value for the initial ACT measurement after the start of dosing for all interventions was 379 sec (median 338 sec; 5 th percentile-95 th percentile 238 to 675 sec). The mean ACT value per intervention over all measurements taken during the procedure was 416 sec (median 390 sec; 5 th percentile-95 th percentile 261 to 698 sec). About 65% of patients had ACTs within the recommended range of 300 to 450 seconds throughout the procedure. The investigators did not achieve anticoagulation within the recommended range in about 23% of patients. However, in this small sample, patients with ACTs below 300 seconds did not have more coronary thrombotic events, and patients with ACTs over 450 seconds did not have higher bleeding rates.

Acute procedural success was defined as lack of death, emergent coronary artery bypass graft (CABG), or Q-wave myocardial infarction. Acute procedural success was reported in 98.2% of patients who underwent PCIs with argatroban anticoagulation compared with 94.3% of historical control patients anticoagulated with heparin (p = NS). Among the 112 interventions, 2 patients had emergency CABGs, 3 had repeat PTCAs, 4 had non-Q-wave myocardial infarctions, 3 had myocardial ischemia, 1 had an abrupt closure, and 1 had an impending closure (some patients may have experienced more than 1 event). No patients died.

16 HOW SUPPLIED/STORAGE AND HANDLING

Argatroban in Sodium Chloride Injection is supplied as a single-dose vial containing 50 mg argatroban in 50 mL of aqueous sodium chloride solution (1 mg/mL). The vial is sealed with a gray rubber stopper and a green aluminum flip-off seal.

NDC 16729-430-11 – Package containing one vial of Argatroban in Sodium Chloride injection (each vial contains 50 mg of argatroban).

NDC 16729-430-43 – Package containing 10 vials of Argatroban in Sodium Chloride injection (each vial contains 50 mg of argatroban).

Storage

Store the vials in original cartons at 20ºC to 25ºC (68ºF to 77°F) [see USP Controlled Room Temperature]: excursion permitted between 15°C to 30°C (59°F to 86°F). Do not refrigerate or freeze. Protect from light and store in carton. Do not use if solution is cloudy or contains a precipitate.

17 PATIENT COUNSELING INFORMATION

Inform patients of the risks associated with Argatroban in Sodium Chloride Injection as well as the plan for regular monitoring during administration of the drug.

Specifically inform patients to report:

  • the use of any other products known to affect bleeding [see Drug Interactions (7)] .
  • any medical history that may increase the risk for bleeding, including a history of severe hypertension; recent lumbar puncture or spinal anesthesia; major surgery, especially involving the brain, spinal cord, or eye; hematologic conditions associated with increased bleeding tendencies such as congenital or acquired bleeding disorders and gastrointestinal lesions such as ulcerations.
  • any bleeding signs or symptoms [see Warnings and Precautions (5.1)] .
  • the occurrence of any signs or symptoms of allergic reactions (e.g., airway reactions, skin reactions and vasodilation reactions). [see Adverse Reactions (6.1)] .

Manufactured For:
Accord Healthcare, Inc.,
1009, Slater Road,
Suite 210-B,
Durham, NC 27703,
USA.

Manufactured By:
Intas Pharmaceuticals Limited,
Plot No.: 457, 458,
Village – Matoda,
Bavla Road, Ta. — Sanand,
Dist.- Ahmedabad – 382 210.
India.
10 2465 0 678427

Principal Display Panel — Carton Label

NDC 16729- 430 -43 Rx only

Argatroban in 0.9% Sodium Chloride Injection

50 mg/50 mL (1 mg/mL)

For Intravenous Infusion Only.

Do not dilute prior to administration.

Discard Unused Portion.

10 Single Dose Vials

Principal Display Panel -- Carton Label
(click image for full-size original)

Principal Display Panel — Carton Label

Principal Display Panel — Vial Label

NDC 16729- 430 -11 Rx only

Argatroban in 0.9% Sodium Chloride Injection

50 mg/50 mL (1 mg/mL)

For Intravenous Infusion Only.

Do not dilute prior to administration.

Single Dose Vial. Discard Unused Portion.

Principal Display Panel -- Vial Label
(click image for full-size original)

Principal Display Panel — Vial Label

Principal Display Panel — Carton Label

NDC 16729- 430 -11 Rx only

Argatroban in 0.9%
Sodium Chloride Injection

50 mg/50 mL
(1 mg/mL)

For Intravenous Infusion Only.

Do not dilute prior to
administration.

Single Dose Vial. Discard Unused Portion.

Principal Display Panel -- Carton Label
(click image for full-size original)
ARGATROBAN argatroban injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:16729-430
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ARGATROBAN (ARGATROBAN ANHYDROUS) ARGATROBAN 1 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE 9 mg in 1 mL
SORBITOL 3 mg in 1 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:16729-430-43 10 VIAL, SINGLE-USE in 1 CARTON contains a VIAL, SINGLE-USE
1 50 mL in 1 VIAL, SINGLE-USE This package is contained within the CARTON (16729-430-43)
2 NDC:16729-430-11 1 VIAL, SINGLE-USE in 1 CARTON contains a VIAL, SINGLE-USE
2 50 mL in 1 VIAL, SINGLE-USE This package is contained within the CARTON (16729-430-11)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA212035 10/07/2021
Labeler — Accord Healthcare Inc. (604222237)
Establishment
Name Address ID/FEI Operations
Intas Pharmaceuticals Limited 725927649 manufacture (16729-430), analysis (16729-430)

Revised: 11/2022 Accord Healthcare Inc.

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