Heparin Sodium: Package Insert and Label Information (Page 3 of 4)

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Heparin interacts with the naturally occurring plasma protein, Antithrombin III, to induce a conformational change, which markedly enhances the serine protease activity of Antithrombin III, thereby inhibiting the activated coagulation factors involved in the clotting sequence, particularly Xa and IIa. Small amounts of heparin inhibit Factor Xa, and larger amounts inhibit thrombin (Factor IIa). Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor. Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots.

12.2 Pharmacodynamics

Various times (activated clotting time, activated partial thromboplastin time, prothrombin time, whole blood clotting time) are prolonged by full therapeutic doses of heparin; in most cases, they are not measurably affected by low doses of heparin. The bleeding time is usually unaffected by heparin.

12.3 Pharmacokinetics

Absorption

Heparin is not absorbed through the gastrointestinal tract and therefore administered via parenteral route. Peak plasma concentration and the onset of action are achieved immediately after intravenous administration.

Distribution

Heparin is highly bound to antithrombin, fibrinogens, globulins, serum proteases and lipoproteins. The volume of distribution is 0.07 L/kg.

Elimination

Metabolism

Heparin does not undergo enzymatic degradation.

Excretion

Heparin is mainly cleared from the circulation by liver and reticuloendothelial cells mediated uptake into extravascular space. Heparin undergoes biphasic clearance, a) rapid saturable clearance (zero order process due to binding to proteins, endothelial cells and macrophage) and b) slower first order elimination. The plasma half-life is dose-dependent and it ranges from 0.5 to 2 h.

Specific Populations

Geriatric patients

Patients over 60 years of age, following similar doses of heparin, may have higher plasma levels of heparin and longer activated partial thromboplastin times (APTTs) compared with patients under 60 years of age [see Use in Specific Populations (8.5) ].

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals have been performed to evaluate carcinogenic potential of heparin. Also, no reproduction studies in animals have been performed concerning mutagenesis or impairment of fertility.

16 HOW SUPPLIED/STORAGE AND HANDLING

Heparin Sodium Injection preserved with benzyl alcohol is available in the following strengths and package sizes in single-dose vials:

DESCRIPTION

NDC

1,000 USP units/mL

1 vial: 1,000 USP units/mL, single-dose* 0641-0391-37

25 vials: 1,000 USP units/mL, single-dose*

0641-0391-12

5,000 USP units/mL

1 vial: 5,000 USP units/mL, single-dose* 0641-0400-37

25 vials: 5,000 USP units/mL, single-dose*

0641-0400-12

10,000 USP units/mL

1 vial: 10,000 USP units/mL, single-dose* 0641-0410-37

25 vials: 10,000 USP units/mL, single-dose*

0641-0410-12

*Discard unused portion

Heparin Sodium Injection preserved with benzyl alcohol is available in the following strengths and package sizes in multiple-dose vials:

DESCRIPTION

NDC

1,000 USP units/mL

1 vial: 30,000 USP units/30 mL, multiple-dose

0641-2450-30

25 vials: 30,000 USP units/30 mL, multiple-dose

0641-2450-55

5,000 USP units/mL

1 vial: 50,000 USP units/10 mL, multiple-dose

0641-2460-30

25 vials: 50,000 USP units/10 mL, multiple-dose

0641-2460-55

Heparin Sodium Injection preservative-free is available in the following strengths and package sizes in single-dose prefilled syringes:

DESCRIPTION

NDC

5,000 USP units/mL

1 Syringe: 5,000 USP units/mL, single-dose*

0641-6199-01

10 Syringes: 5,000 USP units/mL, single-dose*

0641-6199-10

5,000 USP units/0.5 mL
1 Syringe: 5,000 USP units/0.5 mL, single-dose* 0641-6204-01
10 Syringes: 5,000 USP units/0.5 mL, single-dose* 0641-6204-10

*Discard unused portion

Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Hemorrhage
Inform patients that it may take them longer than usual to stop bleeding, that they may bruise and/or bleed more easily when they are treated with heparin, and that they should report any unusual bleeding or bruising to their physician. Hemorrhage can occur at virtually any site in patients receiving heparin. Fatal hemorrhages have occurred [see Warnings and Precautions (5.2) ].

Prior to Surgery
Advise patients to inform physicians and dentists that they are receiving heparin before any surgery is scheduled [see Warnings and Precautions (5.2) ].

Heparin-Induced Thrombocytopenia
Inform patients of the risk of heparin-induced thrombocytopenia (HIT). HIT may progress to the development of venous and arterial thromboses, a condition known as heparin-induced thrombocytopenia and thrombosis (HITT). HIT and HITT can occur up to several weeks after the discontinuation of heparin therapy [see Warnings and Precautions (5.3) ].

Hypersensitivity
Inform patients that generalized hypersensitivity reactions have been reported. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin [see Warnings and Precautions (5.8), Adverse Reactions (6.1)].

Other Medications
Because of the risk of hemorrhage, advise patients to inform their physicians and dentists of all medications they are taking, including non-prescription medications, and before starting any new medication [see Drug Interactions (7.1) ].

Manufactured by:
Hikma Pharmaceuticals USA Inc.
Eatontown, NJ 07724 USA

Revised February 2020

462-274-16

PRINCIPAL DISPLAY PANEL — 1,000 USP units/mL vial

NOT for
Lock
Flush
Rx only
1 mL Vial
NDC 0641-0391-37
Heparin
Sodium Inj., USP
1,000
USP units/mL
FROM
PORCINE
INTESTINESFOR IV OR SC USE

vial
(click image for full-size original)

NDC 0641-0391-12 Rx only
Heparin
Sodium Injection, USP
1,000 USP units/mL
For Intravenous or
Subcutaneous Use
25 x 1 mL Vials

shelfpack
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 5,000 USP units/mL vial

NOT for
Lock
Flush

Rx only
1 mL Vial
NDC 0641-0400-37
Heparin
Sodium Inj., USP
5,000
USP units/mL
FROM
PORCINE
INTESTINESFOR IV OR SC USE

vial
(click image for full-size original)

NDC 0641-0400-12 Rx only
Heparin
Sodium Injection, USP
5,000 USP units/mL
For Intravenous or
Subcutaneous Use25 x 1 mL Vials

sp
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 10,000 USP units/mL vial

NOT for
Lock
Flush
Rx only
1 mL Vial
NDC 0641-0410-37
Heparin
Sodium Inj., USP
10,000
USP units/mL
FROM
PORCINE
INTESTINESFOR IV OR SC USE

vial
(click image for full-size original)

NDC 0641-0410-12 Rx only
Heparin
Sodium Injection, USP
10,000 USP units/mL
For Intravenous or
Subcutaneous Use
25 x 1 mL Vials

sp
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 50,000 USP units/10 mL vial

NOT for Lock Flush
Heparin
Sodium Injection, USP
50,000 USP Units/10 mL
(5,000 USP Units/mL)
For Intravenous or Subcutaneous Use10 mL Multiple Dose Vial

vial
(click image for full-size original)

NDC 0641-2460-55 Rx only
Heparin
Sodium Injection, USP
50,000 USP Units/10 mL
(5,000 USP Units/mL)
For Intravenous or Subcutaneous Use25 x 10 mL Multiple Dose Vials

sp
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 30,000 USP units/30 mL vial

NOT for Lock Flush
Heparin
Sodium Injection, USP
30,000 USP Units/30 mL
(1,000 USP Units/mL)
For Intravenous or Subcutaneous Use30 mL Multiple Dose Vial

vial
(click image for full-size original)

NDC 0641-2450-55 Rx only
Heparin
Sodium Injection, USP
30,000 USP Units/30 mL
(1,000 USP Units/mL)
For Intravenous or Subcutaneous Use25 x 30 mL Multiple Dose Vials

sp
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 5,000 USP units/0.5 mL prefilled syringe

0.5 mL Single Dose Syringe NOT for Lock Flush Rx only
Heparin
Sodium Injection, USP
5,000
USP units/0.5 mL
For IV or SC Use
Preservative-Free NDC 0641-6204-01

syringe
(click image for full-size original)

NOT for Lock Flush
Rx only
NDC 0641-6204-10
Heparin
Sodium Injection, USP
5,000
USP units/0.5 mL
10 x 0.5 mL Prefilled Single Dose Syringes
For Intravenous or
Subcutaneous Use
Preservative-Free
From Porcine Intestines

carton
(click image for full-size original)

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